Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The multiple links between actin and mitochondria

Nature Reviews Molecular Cell Biology volume 24, pages 651–667 (2023)Cite this article

Subjects

A Publisher Correction to this article was published on 28 June 2023

This article has been updated

Abstract

Actin plays many well-known roles in cells, and understanding any specific role is often confounded by the overlap of multiple actin-based structures in space and time. Here, we review our rapidly expanding understanding of actin in mitochondrial biology, where actin plays multiple distinct roles, exemplifying the versatility of actin and its functions in cell biology. One well-studied role of actin in mitochondrial biology is its role in mitochondrial fission, where actin polymerization from the endoplasmic reticulum through the formin INF2 has been shown to stimulate two distinct steps. However, roles for actin during other types of mitochondrial fission, dependent on the Arp2/3 complex, have also been described. In addition, actin performs functions independent of mitochondrial fission. During mitochondrial dysfunction, two distinct phases of Arp2/3 complex-mediated actin polymerization can be triggered. First, within 5 min of dysfunction, rapid actin assembly around mitochondria serves to suppress mitochondrial shape changes and to stimulate glycolysis. At a later time point, at more than 1 h post-dysfunction, a second round of actin polymerization prepares mitochondria for mitophagy. Finally, actin can both stimulate and inhibit mitochondrial motility depending on the context. These motility effects can either be through the polymerization of actin itself or through myosin-based processes, with myosin 19 being an important mitochondrially attached myosin. Overall, distinct actin structures assemble in response to diverse stimuli to affect specific changes to mitochondria.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Actin-based structures.
Fig. 2: Mitochondrial structure and dynamics.
Fig. 3: Actin and mitochondrial fission.
Fig. 4: Two types of actin induced by mitochondrial damage.
Fig. 5: Actin and mitochondrial motility.

Similar content being viewed by others

Change history

References

  1. De Vos, K. J., Allan, V. J., Grierson, A. J. & Sheetz, M. P. Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission. Curr. Biol. 15, 678–683 (2005). This paper is the first to clearly show an effect of actin on mitochondrial division, and also shows that mitochondrial depolarization does not cause rapid mitochondrial fission.

    Article  PubMed  Google Scholar 

  2. Picard, M. & Shirihai, O. S. Mitochondrial signal transduction. Cell Metab. 34, 1620–1653 (2022). An excellent recent review on the diverse functions of mammalian mitochondria.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Blanchoin, L., Boujemaa-Paterski, R., Sykes, C. & Plastino, J. Actin dynamics, architecture, and mechanics in cell motility. Physiol. Rev. 94, 235–263 (2014).

    Article  CAS  PubMed  Google Scholar 

  4. Posern, G. & Treisman, R. Actin’ together: serum response factor, its cofactors and the link to signal transduction. Trends Cell Biol. 16, 588–596 (2006).

    Article  CAS  PubMed  Google Scholar 

  5. Jungblut, A., Hopfner, K. P. & Eustermann, S. Megadalton chromatin remodelers: common principles for versatile functions. Curr. Opin. Struct. Biol. 64, 134–144 (2020).

    Article  CAS  PubMed  Google Scholar 

  6. Kaksonen, M. & Roux, A. Mechanisms of clathrin-mediated endocytosis. Nat. Rev. Mol. Cell Biol. 19, 313–326 (2018).

    Article  CAS  PubMed  Google Scholar 

  7. Krause, M. & Gautreau, A. Steering cell migration: lamellipodium dynamics and the regulation of directional persistence. Nat. Rev. Mol. Cell Biol. 15, 577–590 (2014).

    Article  CAS  PubMed  Google Scholar 

  8. Pollard, T. D. Actin and actin-binding proteins. Cold Spring Harb. Perspect. Biol. https://doi.org/10.1101/cshperspect.a018226 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gautreau, A. M., Fregoso, F. E., Simanov, G. & Dominguez, R. Nucleation, stabilization, and disassembly of branched actin networks. Trends Cell Biol. 32, 421–432 (2022).

    Article  CAS  PubMed  Google Scholar 

  10. Dominguez, R. The WH2 domain and actin nucleation: necessary but insufficient. Trends Biochem. Sci. 41, 478–490 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Quinlan, M. E. Direct interaction between two actin nucleators is required in Drosophila oogenesis. Development 140, 4417–4425 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vafai, S. B. & Mootha, V. K. Mitochondrial disorders as windows into an ancient organelle. Nature 491, 374–383 (2012). We regard this review as a ‘classic’, providing clear insights into many aspects of mitochondrial biology that are still relevant 11 years later.

    Article  CAS  PubMed  Google Scholar 

  13. Kukat, C. et al. Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid. Proc. Natl Acad. Sci. USA 112, 11288–11293 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bogenhagen, D. & Clayton, D. A. The number of mitochondrial deoxyribonucleic acid genomes in mouse L and human HeLa cells. Quantitative isolation of mitochondrial deoxyribonucleic acid. J. Biol. Chem. 249, 7991–7995 (1974).

    Article  CAS  PubMed  Google Scholar 

  15. Satoh, M. & Kuroiwa, T. Organization of multiple nucleoids and DNA molecules in mitochondria of a human cell. Exp. Cell Res. 196, 137–140 (1991).

    Article  CAS  PubMed  Google Scholar 

  16. Rieger, B., Arroum, T., Borowski, M. T., Villalta, J. & Busch, K. B. Mitochondrial F(1) F(O) ATP synthase determines the local proton motive force at cristae rims. EMBO Rep. 22, e52727 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wolf, D. M. et al. Individual cristae within the same mitochondrion display different membrane potentials and are functionally independent. EMBO J. 38, e101056 (2019). An elegant study showing the variation in polarization between neighbouring cristae, suggesting that a single mitochondrion can have considerable functional diversity along its length.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tan, J. X. & Finkel, T. Mitochondria as intracellular signaling platforms in health and disease. J. Cell Biol. https://doi.org/10.1083/jcb.202002179 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Singh, R., Letai, A. & Sarosiek, K. Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat. Rev. Mol. Cell Biol. 20, 175–193 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wu, H., Carvalho, P. & Voeltz, G. K. Here, there, and everywhere: the importance of ER membrane contact sites. Science https://doi.org/10.1126/science.aan5835 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Csordás, G., Weaver, D. & Hajnóczky, G. Endoplasmic reticulum-mitochondrial contactology: structure and signaling functions. Trends Cell Biol. 28, 523–540 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Veliova, M., Petcherski, A., Liesa, M. & Shirihai, O. S. The biology of lipid droplet-bound mitochondria. Semin. Cell Dev. Biol. 108, 55–64 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wong, Y. C., Kim, S., Peng, W. & Krainc, D. Regulation and function of mitochondria-lysosome membrane contact sites in cellular homeostasis. Trends Cell Biol. 29, 500–513 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nagashima, S. et al. Golgi-derived PI(4)P-containing vesicles drive late steps of mitochondrial division. Science 367, 1366–1371 (2020).

    Article  CAS  PubMed  Google Scholar 

  25. Picard, M. et al. Trans-mitochondrial coordination of cristae at regulated membrane junctions. Nat. Commun. 6, 6259 (2015).

    Article  CAS  PubMed  Google Scholar 

  26. Glancy, B. et al. Power grid protection of the muscle mitochondrial reticulum. Cell Rep. 19, 487–496 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chan, D. C. Mitochondrial dynamics and its involvement in disease. Annu. Rev. Pathol. Mech. Dis. 15, 235–259 (2020).

    Article  CAS  Google Scholar 

  28. Yapa, N. M. B., Lisnyak, V., Reljic, B. & Ryan, M. T. Mitochondrial dynamics in health and disease. FEBS Lett. 595, 1184–1204 (2021).

    Article  CAS  PubMed  Google Scholar 

  29. Legros, F., Lombès, A., Frachon, P. & Rojo, M. Mitochondrial fusion in human cells is efficient, requires the inner membrane potential, and is mediated by mitofusins. Mol. Biol. Cell 13, 4343–4354 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Song, Z., Chen, H., Fiket, M., Alexander, C. & Chan, D. C. OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L. J. Cell Biol. 178, 749–755 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Abrisch, R. G., Gumbin, S. C., Wisniewski, B. T., Lackner, L. L. & Voeltz, G. K. Fission and fusion machineries converge at ER contact sites to regulate mitochondrial morphology. J. Cell Biol. https://doi.org/10.1083/jcb.201911122 (2020). This paper shows that the ERMC sites might mark sites of both MFN1 and DRP1 to these sites, and that rescue of mitochondrial membrane potential can happen at these sites.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Gao, S. & Hu, J. Mitochondrial fusion: the machineries in and out. Trends Cell Biol. 31, 62–74 (2021).

    Article  CAS  PubMed  Google Scholar 

  33. Kraus, F., Roy, K., Pucadyil, T. J. & Ryan, M. T. Function and regulation of the divisome for mitochondrial fission. Nature 590, 57–66 (2021).

    Article  CAS  PubMed  Google Scholar 

  34. Lewis, S. C., Uchiyama, L. F. & Nunnari, J. ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells. Science 353, aaf5549 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Friedman, J. R. et al. ER tubules mark sites of mitochondrial division. Science 334, 358–362 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Hatch, A. L., Gurel, P. S. & Higgs, H. N. Novel roles for actin in mitochondrial fission. J. Cell Sci. 127, 4549–4560 (2014).

    PubMed  PubMed Central  Google Scholar 

  37. Jang, W. et al. Endosomal lipid signaling reshapes the endoplasmic reticulum to control mitochondrial function. Science 378, eabq5209 (2022).

    Article  CAS  PubMed  Google Scholar 

  38. Wong, Y. C., Ysselstein, D. & Krainc, D. Mitochondria-lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis. Nature 554, 382–386 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lee, J. E., Westrate, L. M., Wu, H., Page, C. & Voeltz, G. K. Multiple dynamin family members collaborate to drive mitochondrial division. Nature 540, 139–143 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Fonseca, T. B., Sánchez-Guerrero, Á., Milosevic, I. & Raimundo, N. Mitochondrial fission requires DRP1 but not dynamins. Nature 570, E34–E42 (2019).

    Article  CAS  PubMed  Google Scholar 

  41. Twig, G. et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 27, 433–446 (2008). This paper shows evidence for rapid sequential fusion then fission (termed ‘kiss-and-run’), and daughter mitochondria after fission can have different membrane potentials, with the lower potential daughter undergoing mitophagy.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Liu, X., Weaver, D., Shirihai, O. & Hajnóczky, G. Mitochondrial ‘kiss-and-run’: interplay between mitochondrial motility and fusion-fission dynamics. EMBO J. 28, 3074–3089 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Itoh, T., Toh, E. A. & Matsui, Y. Mmr1p is a mitochondrial factor for Myo2p-dependent inheritance of mitochondria in the budding yeast. EMBO J. 23, 2520–2530 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Swayne, T. C. et al. Role for cER and Mmr1p in anchorage of mitochondria at sites of polarized surface growth in budding yeast. Curr. Biol. 21, 1994–1999 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chernyakov, I., Santiago-Tirado, F. & Bretscher, A. Active segregation of yeast mitochondria by Myo2 is essential and mediated by Mmr1 and Ypt11. Curr. Biol. 23, 1818–1824 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Schwarz, T. L. Mitochondrial trafficking in neurons. Cold Spring Harb. Perspect. Biol. https://doi.org/10.1101/cshperspect.a011304 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Sato, O. et al. Mitochondria-associated myosin 19 processively transports mitochondria on actin tracks in living cells. J. Biol. Chem. 298, 101883 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ušaj, M. & Henn, A. Kinetic adaptation of human Myo19 for active mitochondrial transport to growing filopodia tips. Sci. Rep. 7, 11596 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Moore, A. S. et al. Actin cables and comet tails organize mitochondrial networks in mitosis. Nature 591, 659–664 (2021). Two types of novel mitochondrially associated actin during mitosis are revealed here: cables that tether mitochondria and clouds that can result in rapid mitochondrial motility.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mishra, P. & Chan, D. C. Mitochondrial dynamics and inheritance during cell division, development and disease. Nat. Rev. Mol. Cell Biol. 15, 634–646 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Misgeld, T. & Schwarz, T. L. Mitostasis in neurons: maintaining mitochondria in an extended cellular architecture. Neuron 96, 651–666 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Rambold, A. S., Kostelecky, B., Elia, N. & Lippincott-Schwartz, J. Tubular network formation protects mitochondria from autophagosomal degradation during nutrient starvation. Proc. Natl Acad. Sci. USA 108, 10190–10195 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Huang, X. et al. Kissing and nanotunneling mediate intermitochondrial communication in the heart. Proc. Natl Acad. Sci. USA 110, 2846–2851 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lavorato, M. et al. Increased mitochondrial nanotunneling activity, induced by calcium imbalance, affects intermitochondrial matrix exchanges. Proc. Natl Acad. Sci. 114, E849–E858 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Cogliati, S., Enriquez, J. A. & Scorrano, L. Mitochondrial cristae: where beauty meets functionality. Trends Biochem. Sci. 41, 261–273 (2016).

    Article  CAS  PubMed  Google Scholar 

  56. MacVicar, T. & Langer, T. OPA1 processing in cell death and disease — the long and short of it. J. Cell Sci. 129, 2297–2306 (2016).

    CAS  PubMed  Google Scholar 

  57. Soubannier, V. et al. A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr. Biol. 22, 135–141 (2012).

    Article  CAS  PubMed  Google Scholar 

  58. Hughes, A. L., Hughes, C. E., Henderson, K. A., Yazvenko, N. & Gottschling, D. E. Selective sorting and destruction of mitochondrial membrane proteins in aged yeast. eLife https://doi.org/10.7554/eLife.13943 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  59. König, T. et al. MIROs and DRP1 drive mitochondrial-derived vesicle biogenesis and promote quality control. Nat. Cell Biol. 23, 1271–1286 (2021). A technical tour-de-force, defining many aspects of mitochondrially derived vesicle formation in mammalian cells.

    Article  PubMed  Google Scholar 

  60. Picard, M., Hepple, R. T. & Burelle, Y. Mitochondrial functional specialization in glycolytic and oxidative muscle fibers: tailoring the organelle for optimal function. Am. J. Physiol. Cell Physiol. 302, C629–C641 (2012).

    Article  CAS  PubMed  Google Scholar 

  61. Selvaraj, V., Stocco, D. M. & Clark, B. J. Current knowledge on the acute regulation of steroidogenesis. Biol. Reprod. 99, 13–26 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Rosen, E. D. & Spiegelman, B. M. What we talk about when we talk about fat. Cell 156, 20–44 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Morio, B., Panthu, B., Bassot, A. & Rieusset, J. Role of mitochondria in liver metabolic health and diseases. Cell Calcium 94, 102336 (2021).

    Article  CAS  PubMed  Google Scholar 

  64. Pavlova, N. N., Zhu, J. & Thompson, C. B. The hallmarks of cancer metabolism: still emerging. Cell Metab. 34, 355–377 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Rausser, S. et al. Mitochondrial phenotypes in purified human immune cell subtypes and cell mixtures. eLife https://doi.org/10.7554/eLife.70899 (2021). An elegant study showing mitochondrial variation in humans on a week-to-week basis.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Pagliarini, D. J. et al. A mitochondrial protein compendium elucidates complex I disease biology. Cell 134, 112–123 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Fecher, C. et al. Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity. Nat. Neurosci. 22, 1731–1742 (2019).

    Article  CAS  PubMed  Google Scholar 

  68. Stauch, K. L., Purnell, P. R. & Fox, H. S. Quantitative proteomics of synaptic and nonsynaptic mitochondria: insights for synaptic mitochondrial vulnerability. J. Proteome Res. 13, 2620–2636 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. El Bacha, T., Luz, M. & Da Poian, A. Dynamic adaptation of nutrient utilization in humans. Nat. Educ. 3, 11 (2010).

    Google Scholar 

  70. Alan, L. & Scorrano, L. Shaping fuel utilization by mitochondria. Curr. Biol. 32, R618–R623 (2022).

    Article  CAS  PubMed  Google Scholar 

  71. Picard, M., Shirihai, O. S., Gentil, B. J. & Burelle, Y. Mitochondrial morphology transitions and functions: implications for retrograde signaling. Am. J. Physiol. Regul. Integr. Comp. Physiol. 304, R393–R406 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Steiner, P., Luckner, M., Kerschbaum, H., Wanner, G. & Lütz-Meindl, U. Ionic stress induces fusion of mitochondria to 3-D networks: An electron tomography study. J. Struct. Biol. 204, 52–63 (2018).

    Article  CAS  PubMed  Google Scholar 

  73. Kage, F., Vicente-Manzanares, M., McEwan, B. C., Kettenbach, A. N. & Higgs, H. N. Myosin II proteins are required for organization of calcium-induced actin networks upstream of mitochondrial division. Mol. Biol. Cell 33, ar63 (2022). Figure 8 of this paper shows clear evidence for morphological heterogeneity between perinuclear and peripheral mitochondria in the same cell and differential influence of myosin II on these two populations.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Fischer, T. D., Dash, P. K., Liu, J. & Waxham, M. N. Morphology of mitochondria in spatially restricted axons revealed by cryo-electron tomography. PLoS Biol. 16, e2006169 (2018). This paper shows the ability of mitochondria to narrow to 20 nm diameter in certain situations.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Mishra, P., Carelli, V., Manfredi, G. & Chan, D. C. Proteolytic cleavage of Opa1 stimulates mitochondrial inner membrane fusion and couples fusion to oxidative phosphorylation. Cell Metab. 19, 630–641 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Chakrabarti, R. et al. INF2-mediated actin polymerization at the ER stimulates mitochondrial calcium uptake, inner membrane constriction, and division. J. Cell Biol. 217, 251–268 (2017). Comprehensive study on CIA-induced mitochondrial calcium increase.

    Article  PubMed  Google Scholar 

  77. Helle, S. C. J. et al. Mechanical force induces mitochondrial fission. eLife https://doi.org/10.7554/eLife.30292 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Kleele, T. et al. Distinct fission signatures predict mitochondrial degradation or biogenesis. Nature 593, 435–439 (2021). A seminal study showing that two mechanistically distinct mitochondrial fission processes exist in mammalian cells.

    Article  CAS  PubMed  Google Scholar 

  79. Yamashita, S. I. et al. Mitochondrial division occurs concurrently with autophagosome formation but independently of Drp1 during mitophagy. J. Cell Biol. 215, 649–665 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shimura, D. et al. Protective mitochondrial fission induced by stress-responsive protein GJA1-20k. eLife https://doi.org/10.7554/eLife.69207 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Fu, D. & Lippincott-Schwartz, J. Monitoring the effects of pharmacological reagents on mitochondrial morphology. Curr. Protoc. Cell Biol. 79, e45 (2018).

    Article  PubMed  Google Scholar 

  82. Li, S. et al. Transient assembly of F-actin on the outer mitochondrial membrane contributes to mitochondrial fission. J. Cell Biol. 208, 109–123 (2015). First report of rapid actin polymerization around dysfunctional mitochondria (ADA).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Mageswaran, S. K. et al. Nanoscale details of mitochondrial fission revealed by cryo-electron tomography. bioRxiv https://doi.org/10.1101/2021.12.13.472487 (2021).

    Article  Google Scholar 

  84. Minamikawa, T., Williams, D. A., Bowser, D. N. & Nagley, P. Mitochondrial permeability transition and swelling can occur reversibly without inducing cell death in intact human cells. Exp. Cell Res. 246, 26–37 (1999).

    Article  CAS  PubMed  Google Scholar 

  85. Liu, X. & Hajnóczky, G. Altered fusion dynamics underlie unique morphological changes in mitochondria during hypoxia-reoxygenation stress. Cell Death Differ. 18, 1561–1572 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Miyazono, Y. et al. Uncoupled mitochondria quickly shorten along their long axis to form indented spheroids, instead of rings, in a fission-independent manner. Sci. Rep. 8, 350 (2018). A correlative fluorescence microscopy/electron microscopy study showing that mitochondrial depolarization does not result in rapid fission but in IMM rearrangement leading to circular mitochondria with an intact OMM.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Fung, T. S., Ji, W.-K., Higgs, H. N. & Chakrabarti, R. Two distinct actin filament populations have effects on mitochondria, with differences in stimuli and assembly factors. J. Cell Sci. 132, jcs234435 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Fung, T. S. et al. Parallel kinase pathways stimulate actin polymerization at depolarized mitochondria. Curr. Biol. 32, 1577–1592.e8 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Guha, S. et al. Selective disruption of Drp1-independent mitophagy and mitolysosome trafficking by an Alzheimer’s disease relevant tau modification in a novel Caenorhabditis elegans model. Genetics https://doi.org/10.1093/genetics/iyac104 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Korobova, F., Ramabhadran, V. & Higgs, H. N. An actin-dependent step in mitochondrial fission mediated by the ER-associated formin INF2. Science 339, 464–467 (2013).

    Article  CAS  PubMed  Google Scholar 

  91. Ji, W. K., Hatch, A. L., Merrill, R. A., Strack, S. & Higgs, H. N. Actin filaments target the oligomeric maturation of the dynamin GTPase Drp1 to mitochondrial fission sites. eLife 4, e11553 (2015). Study showing CIA-mediated recruitment of DRP1 to mitochondrial fission sites.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Yang, C. & Svitkina, T. M. Ultrastructure and dynamics of the actin-myosin II cytoskeleton during mitochondrial fission. Nat. Cell Biol. 21, 603–613 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Shao, X., Li, Q., Mogilner, A., Bershadsky, A. D. & Shivashankar, G. V. Mechanical stimulation induces formin-dependent assembly of a perinuclear actin rim. Proc. Natl Acad. Sci. USA 112, E2595–E2601 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Wales, P. et al. Calcium-mediated actin reset (CaAR) mediates acute cell adaptations. eLife https://doi.org/10.7554/eLife.19850 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Manor, U. et al. A mitochondria-anchored isoform of the actin-nucleating spire protein regulates mitochondrial division. eLife https://doi.org/10.7554/eLife.08828 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  96. DuBoff, B., Götz, J. & Feany, M. B. Tau promotes neurodegeneration via DRP1 mislocalization in vivo. Neuron 75, 618–632 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Korobova, F., Gauvin, T. J. & Higgs, H. N. A role for myosin II in mammalian mitochondrial fission. Curr. Biol. 24, 409–414 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Coscia, S. M. et al. Myo19 tethers mitochondria to endoplasmic reticulum-associated actin to promote mitochondrial fission. J. Cell Sci. https://doi.org/10.1242/jcs.260612 (2023).

    Article  PubMed  Google Scholar 

  99. Lin, S. et al. Fascin controls metastatic colonization and mitochondrial oxidative phosphorylation by remodeling mitochondrial actin filaments. Cell Rep. 28, 2824–2836.e28 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Cho, B. et al. Constriction of the mitochondrial inner compartment is a priming event for mitochondrial division. Nat. Commun. 8, 15754 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  101. Hatch, A. L., Ji, W. K., Merrill, R. A., Strack, S. & Higgs, H. N. Actin filaments as dynamic reservoirs for Drp1 recruitment. Mol. Biol. Cell 27, 3109–3121 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Liu, A., Kage, F. & Higgs, H. N. Mff oligomerization is required for Drp1 activation and synergy with actin filaments during mitochondrial division. Mol. Biol. Cell https://doi.org/10.1091/mbc.E21-04-0224 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Ji, W. K. et al. Receptor-mediated Drp1 oligomerization on endoplasmic reticulum. J. Cell Biol. 216, 4123–4139 (2017). Study showing evidence for ER-bound pools of both MFF and FIS1 as well as actin-stimulated DRP1 recruitment to ER.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Liu, R. & Chan, D. C. The mitochondrial fission receptor Mff selectively recruits oligomerized Drp1. Mol. Biol. Cell 26, 4466–4477 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Denton, R. M. Regulation of mitochondrial dehydrogenases by calcium ions. Biochim. Biophys. Acta 1787, 1309–1316 (2009).

    Article  CAS  PubMed  Google Scholar 

  106. Ashrafi, G., de Juan-Sanz, J., Farrell, R. J. & Ryan, T. A. Molecular tuning of the axonal mitochondrial Ca(2+) uniporter ensures metabolic flexibility of neurotransmission. Neuron 105, 678–687.e5 (2020).

    Article  CAS  PubMed  Google Scholar 

  107. Anand, R. et al. The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. J. Cell Biol. 204, 919–929 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Billington, N., Wang, A., Mao, J., Adelstein, R. S. & Sellers, J. R. Characterization of three full-length human nonmuscle myosin II paralogs. J. Biol. Chem. 288, 33398–33410 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Laporte, D., Coffman, V. C., Lee, I. J. & Wu, J. Q. Assembly and architecture of precursor nodes during fission yeast cytokinesis. J. Cell Biol. 192, 1005–1021 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Pollard, L. W. et al. Fission yeast myosin Myo2 is down-regulated in actin affinity by light chain phosphorylation. Proc. Natl Acad. Sci. USA 114, E7236–E7244 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Shutova, M. S., Spessott, W. A., Giraudo, C. G. & Svitkina, T. Endogenous species of mammalian nonmuscle myosin IIA and IIB include activated monomers and heteropolymers. Curr. Biol. 24, 1958–1968 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Pfender, S., Kuznetsov, V., Pleiser, S., Kerkhoff, E. & Schuh, M. Spire-type actin nucleators cooperate with Formin-2 to drive asymmetric oocyte division. Curr. Biol. 21, 955–960 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Duan, X. et al. Dynamic organelle distribution initiates actin-based spindle migration in mouse oocytes. Nat. Commun. 11, 277 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Sellers, J. R. & Heissler, S. M. Nonmuscle myosin-2 isoforms. Curr. Biol. 29, R275–R278 (2019).

    Article  CAS  PubMed  Google Scholar 

  115. Romani, P. et al. Mitochondrial fission links ECM mechanotransduction to metabolic redox homeostasis and metastatic chemotherapy resistance. Nat. Cell Biol. 24, 168–180 (2022).

    Article  CAS  PubMed  Google Scholar 

  116. Nishimura, A. et al. Hypoxia-induced interaction of filamin with Drp1 causes mitochondrial hyperfission-associated myocardial senescence. Sci. Signal. https://doi.org/10.1126/scisignal.aat5185 (2018).

    Article  PubMed  Google Scholar 

  117. Bai, Y. et al. Mitochondrial quality control in cardiac ischemia/reperfusion injury: new insights into mechanisms and implications. Cell. Biol. Toxicol. https://doi.org/10.1007/s10565-022-09716-2 (2022).

    Article  PubMed  Google Scholar 

  118. Pedriali, G. et al. Perspectives on mitochondrial relevance in cardiac ischemia/reperfusion injury. Front. Cell Dev. Biol. 10, 1082095 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  119. Wang, T. F., Zhou, C., Tang, A. H., Wang, S. Q. & Chai, Z. Cellular mechanism for spontaneous calcium oscillations in astrocytes. Acta Pharmacol. Sin. 27, 861–868 (2006).

    Article  CAS  PubMed  Google Scholar 

  120. Zhou, Y. et al. Spontaneous calcium signaling of cartilage cells: from spatiotemporal features to biophysical modeling. FASEB J. 33, 4675–4687 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Labat-de-Hoz, L. & Alonso, M. A. The formin INF2 in disease: progress from 10 years of research. Cell Mol. Life Sci. 77, 4581–4600 (2020).

    Article  CAS  PubMed  Google Scholar 

  122. Zaman, M. & Shutt, T. E. The role of impaired mitochondrial dynamics in MFN2-mediated pathology. Front. Cell Dev. Biol. 10, 858286 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Lamm, K. Y. B. et al. Inverted formin 2 regulates intracellular trafficking, placentation, and pregnancy outcome. eLife https://doi.org/10.7554/eLife.31150 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Zhang, Z. & Yu, J. Nurr1 exacerbates cerebral ischemia-reperfusion injury via modulating YAP-INF2-mitochondrial fission pathways. Int. J. Biochem. Cell Biol. 104, 149–160 (2018).

    Article  CAS  PubMed  Google Scholar 

  125. Chen, Z. et al. INF2 regulates oxidative stress-induced apoptosis in epidermal HaCaT cells by modulating the HIF1 signaling pathway. Biomed. Pharmacother. 111, 151–161 (2019).

    Article  CAS  PubMed  Google Scholar 

  126. Horn, A., Raavicharla, S., Shah, S., Cox, D. & Jaiswal, J. K. Mitochondrial fragmentation enables localized signaling required for cell repair. J. Cell Biol. https://doi.org/10.1083/jcb.201909154 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Murphy, M. P. Understanding and preventing mitochondrial oxidative damage. Biochem. Soc. Trans. 44, 1219–1226 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Suomalainen, A. & Battersby, B. J. Mitochondrial diseases: the contribution of organelle stress responses to pathology. Nat. Rev. Mol. Cell Biol. 19, 77–92 (2018).

    Article  CAS  PubMed  Google Scholar 

  129. Owen, M. R., Doran, E. & Halestrap, A. P. Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem. J. 348, 607–614 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Zhou, M. et al. Myocardial ischemia-reperfusion injury: therapeutics from a mitochondria-centric perspective. Cardiology 146, 781–792 (2021).

    Article  CAS  PubMed  Google Scholar 

  131. Bertholet, A. M. et al. Mitochondrial uncouplers induce proton leak by activating AAC and UCP1. Nature 606, 180–187 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Pickles, S., Vigié, P. & Youle, R. J. Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr. Biol. 28, R170–R185 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Killackey, S. A., Philpott, D. J. & Girardin, S. E. Mitophagy pathways in health and disease. J. Cell Biol. https://doi.org/10.1083/jcb.202004029 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  134. Kast, D. J. & Dominguez, R. The cytoskeleton-autophagy connection. Curr. Biol. 27, R318–R326 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Hu, X. & Mullins, R. D. LC3 and STRAP regulate actin filament assembly by JMY during autophagosome formation. J. Cell Biol. 218, 251–266 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Kruppa, A. J. et al. Myosin VI-dependent actin cages encapsulate parkin-positive damaged mitochondria. Dev. Cell 44, 484–499.e6 (2018). First report of the process we call PDA.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Chakrabarti, R. et al. Mitochondrial dysfunction triggers actin polymerization necessary for rapid glycolytic activation. J. Cell Biol. https://doi.org/10.1083/jcb.202201160 (2022). This paper links peri-mitochondrial actin polymerization to glycolytic regulation upon both actute mitochondrial damage (ADA) and chronic mitochondrial dysfunction.

    Article  PubMed  PubMed Central  Google Scholar 

  138. Hu, H. et al. Phosphoinositide 3-kinase regulates glycolysis through mobilization of aldolase from the actin cytoskeleton. Cell 164, 433–446 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Park, J. S. et al. Mechanical regulation of glycolysis via cytoskeleton architecture. Nature 578, 621–626 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Kondo, H. et al. Single-cell resolved imaging reveals intra-tumor heterogeneity in glycolysis, transitions between metabolic states, and their regulatory mechanisms. Cell Rep. 34, 108750 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Hsieh, C.-W. & Yang, W. Y. Omegasome-proximal PtdIns(4,5)P2 couples F-actin mediated mitoaggregate disassembly with autophagosome formation during mitophagy. Nat. Commun. 10, 969 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  142. Rivers, E. et al. Wiskott Aldrich syndrome protein regulates non-selective autophagy and mitochondrial homeostasis in human myeloid cells. eLife https://doi.org/10.7554/eLife.55547 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  143. Mathiowetz, A. J. et al. An Amish founder mutation disrupts a PI(3)P-WHAMM-Arp2/3 complex-driven autophagosomal remodeling pathway. Mol. Biol. Cell 28, 2492–2507 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Dai, A., Yu, L. & Wang, H. W. WHAMM initiates autolysosome tubulation by promoting actin polymerization on autolysosomes. Nat. Commun. 10, 3699 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  145. Müller, P. M. et al. Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nat. Cell Biol. 22, 498–511 (2020).

    Article  PubMed  Google Scholar 

  146. Pekkurnaz, G., Trinidad, J. C., Wang, X., Kong, D. & Schwarz, T. L. Glucose regulates mitochondrial motility via Milton modification by O-GlcNAc transferase. Cell 158, 54–68 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Basu, H. et al. FHL2 anchors mitochondria to actin and adapts mitochondrial dynamics to glucose supply. J. Cell Biol. https://doi.org/10.1083/jcb.201912077 (2021). Actin-mediated mitochondrial motility arrest in neurons, triggered by increased cytoplasmic glucose.

    Article  PubMed  PubMed Central  Google Scholar 

  148. Shneyer, B. I., Ušaj, M., Wiesel-Motiuk, N., Regev, R. & Henn, A. ROS induced distribution of mitochondria to filopodia by Myo19 depends on a class specific tryptophan in the motor domain. Sci. Rep. 7, 11577 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  149. Shneyer, B. I., Ušaj, M. & Henn, A. Myo19 is an outer mitochondrial membrane motor and effector of starvation-induced filopodia. J. Cell Sci. 129, 543–556 (2016).

    CAS  PubMed  Google Scholar 

  150. Jiao, H. et al. Mitocytosis, a migrasome-mediated mitochondrial quality-control process. Cell 184, 2896–2910.e13 (2021).

    Article  CAS  PubMed  Google Scholar 

  151. Rohn, J. L. et al. Myo19 ensures symmetric partitioning of mitochondria and coupling of mitochondrial segregation to cell division. Curr. Biol. 24, 2598–2605 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Majstrowicz, K. et al. Coordination of mitochondrial and cellular dynamics by the actin-based motor Myo19. J. Cell Sci. https://doi.org/10.1242/jcs.255844 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  153. Shi, P. et al. Mechanical instability generated by Myosin 19 contributes to mitochondria cristae architecture and OXPHOS. Nat. Commun. 13, 2673 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Bocanegra, J. L. et al. The MyMOMA domain of MYO19 encodes for distinct Miro-dependent and Miro-independent mechanisms of interaction with mitochondrial membranes. Cytoskeleton 77, 149–166 (2020).

    Article  CAS  PubMed  Google Scholar 

  155. Lopez-Domenech, G. et al. Miro proteins coordinate microtubule- and actin-dependent mitochondrial transport and distribution. EMBO J. 37, 321–336 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Oeding, S. J. et al. Identification of Miro1 and Miro2 as mitochondrial receptors for myosin XIX. J. Cell Sci. https://doi.org/10.1242/jcs.219469 (2018).

    Article  PubMed  Google Scholar 

  157. Pathak, D., Sepp, K. J. & Hollenbeck, P. J. Evidence that myosin activity opposes microtubule-based axonal transport of mitochondria. J. Neurosci. 30, 8984–8992 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Li, S., Xiong, G. J., Huang, N. & Sheng, Z. H. The cross-talk of energy sensing and mitochondrial anchoring sustains synaptic efficacy by maintaining presynaptic metabolism. Nat. Metab. 2, 1077–1095 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Kruppa, A. J. & Buss, F. Motor proteins at the mitochondria-cytoskeleton interface. J. Cell Sci. https://doi.org/10.1242/jcs.226084 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  160. Chakrabarti, R., Lee, M. & Higgs, H. N. Multiple roles for actin in secretory and endocytic pathways. Curr. Biol. 31, R603–R618 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Lamason, R. L. & Welch, M. D. Actin-based motility and cell-to-cell spread of bacterial pathogens. Curr. Opin. Microbiol. 35, 48–57 (2017).

    Article  CAS  PubMed  Google Scholar 

  162. Boldogh, I. R. et al. Arp2/3 complex and actin dynamics are required for actin-based mitochondrial motility in yeast. Proc. Natl Acad. Sci. USA 98, 3162–3167 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Moore, A. S., Wong, Y. C., Simpson, C. L. & Holzbaur, E. L. Dynamic actin cycling through mitochondrial subpopulations locally regulates the fission-fusion balance within mitochondrial networks. Nat. Commun. 7, 12886 (2016). Shows first evidence of cycling waves of actin clouds around populations of mitochondria.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Danial, N. N. et al. BAD and glucokinase reside in a mitochondrial complex that integrates glycolysis and apoptosis. Nature 424, 952–956 (2003).

    Article  CAS  PubMed  Google Scholar 

  165. Cheng, A. et al. Pancortin-2 interacts with WAVE1 and Bcl-xL in a mitochondria-associated protein complex that mediates ischemic neuronal death. J. Neurosci. 27, 1519–1528 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Kang, R. et al. WAVE1 regulates Bcl-2 localization and phosphorylation in leukemia cells. Leukemia 24, 177–186 (2010).

    Article  CAS  PubMed  Google Scholar 

  167. King, V. L., Leclair, N. K., Coulter, A. M. & Campellone, K. G. The actin nucleation factors JMY and WHAMM enable a rapid Arp2/3 complex-mediated intrinsic pathway of apoptosis. PLoS Genet. 17, e1009512 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Chua, B. T. et al. Mitochondrial translocation of cofilin is an early step in apoptosis induction. Nat. Cell Biol. 5, 1083–1089 (2003).

    Article  CAS  PubMed  Google Scholar 

  169. Rehklau, K. et al. ADF/cofilin proteins translocate to mitochondria during apoptosis but are not generally required for cell death signaling. Cell Death Differ. 19, 958–967 (2012).

    Article  CAS  PubMed  Google Scholar 

  170. Rehklau, K. et al. Cofilin1-dependent actin dynamics control DRP1-mediated mitochondrial fission. Cell Death Dis. 8, e3063 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  171. Li, G. B. et al. Mitochondrial fission and mitophagy depend on cofilin-mediated actin depolymerization activity at the mitochondrial fission site. Oncogene 37, 1485–1502 (2018).

    Article  CAS  PubMed  Google Scholar 

  172. Li, G. B. et al. Mitochondrial translocation of cofilin is required for allyl isothiocyanate-mediated cell death via ROCK1/PTEN/PI3K signaling pathway. Cell Commun. Signal. 11, 50 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Klamt, F. et al. Oxidant-induced apoptosis is mediated by oxidation of the actin-regulatory protein cofilin. Nat. Cell Biol. 11, 1241–1246 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Wabnitz, G. H. et al. Mitochondrial translocation of oxidized cofilin induces caspase-independent necrotic-like programmed cell death of T cells. Cell Death Dis. 1, e58 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Hoffmann, L. et al. Cofilin1 oxidation links oxidative distress to mitochondrial demise and neuronal cell death. Cell Death Dis. 12, 953 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Vögtle, F. N. et al. Global analysis of the mitochondrial N-proteome identifies a processing peptidase critical for protein stability. Cell 139, 428–439 (2009).

    Article  PubMed  Google Scholar 

  177. Calvo, S. E. et al. Comparative analysis of mitochondrial N-termini from mouse, human, and yeast. Mol. Cell. Proteom. 16, 512–523 (2017).

    Article  CAS  Google Scholar 

  178. Fukasawa, Y. et al. MitoFates: improved prediction of mitochondrial targeting sequences and their cleavage sites. Mol. Cell. Proteom. 14, 1113–1126 (2015).

    Article  CAS  Google Scholar 

  179. Bykov, Y. S. et al. Widespread use of unconventional targeting signals in mitochondrial ribosome proteins. EMBO J. 41, e109519 (2022).

    Article  CAS  PubMed  Google Scholar 

  180. Chatterjee, A. et al. MOF Acetyl transferase regulates transcription and respiration in mitochondria. Cell 167, 722–738.e3 (2016).

    Article  CAS  PubMed  Google Scholar 

  181. Reyes, A. et al. Actin and myosin contribute to mammalian mitochondrial DNA maintenance. Nucleic Acids Res. 39, 5098–5108 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Xie, X., Venit, T., Drou, N. & Percipalle, P. In Mitochondria? — Actin regulates mtDNA transcription and is required for mitochondrial quality control. iScience 3, 226–237 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Takahashi, K., Miura, Y., Ohsawa, I., Shirasawa, T. & Takahashi, M. In vitro rejuvenation of brain mitochondria by the inhibition of actin polymerization. Sci. Rep. 8, 15585 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  184. Ulferts, S., Prajapati, B., Grosse, R. & Vartiainen, M. K. Emerging properties and functions of actin and actin filaments inside the nucleus. Cold Spring Harb. Perspect. Biol. https://doi.org/10.1101/cshperspect.a040121 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  185. Lehrer, S. S. Damage to actin filaments by glutaraldehyde: protection by tropomyosin. J. Cell Biol. 90, 459–466 (1981).

    Article  CAS  PubMed  Google Scholar 

  186. Maupin, P. & Pollard, T. D. Improved preservation and staining of HeLa cell actin filaments, clathrin-coated membranes, and other cytoplasmic structures by tannic acid-glutaraldehyde-saponin fixation. J. Cell Biol. 96, 51–62 (1983).

    Article  CAS  PubMed  Google Scholar 

  187. Kudryashev, M., Lepper, S., Baumeister, W., Cyrklaff, M. & Frischknecht, F. Geometric constrains for detecting short actin filaments by cryogenic electron tomography. PMC Biophys. 3, 6 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  188. Svitkina, T. Imaging cytoskeleton components by electron microscopy. Methods Mol. Biol. 2364, 25–52 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  189. Edwards, M. et al. Capping protein regulators fine-tune actin assembly dynamics. Nat. Rev. Mol. Cell Biol. 15, 677–689 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Bombardier, J. P. et al. Single-molecule visualization of a formin-capping protein ‘decision complex’ at the actin filament barbed end. Nat. Commun. 6, 8707 (2015).

    Article  CAS  PubMed  Google Scholar 

  191. Shekhar, S. et al. Formin and capping protein together embrace the actin filament in a ménage à trois. Nat. Commun. 6, 8730 (2015).

    Article  CAS  PubMed  Google Scholar 

  192. Bravo-Cordero, J. J., Magalhaes, M. A., Eddy, R. J., Hodgson, L. & Condeelis, J. Functions of cofilin in cell locomotion and invasion. Nat. Rev. Mol. Cell Biol. 14, 405–415 (2013).

    Article  CAS  PubMed  Google Scholar 

  193. Kotila, T. et al. Mechanism of synergistic actin filament pointed end depolymerization by cyclase-associated protein and cofilin. Nat. Commun. 10, 5320 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  194. Shekhar, S., Chung, J., Kondev, J., Gelles, J. & Goode, B. L. Synergy between cyclase-associated protein and Cofilin accelerates actin filament depolymerization by two orders of magnitude. Nat. Commun. 10, 5319 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  195. Tang, V. W., Nadkarni, A. V. & Brieher, W. M. Catastrophic actin filament bursting by cofilin, Aip1, and coronin. J. Biol. Chem. 295, 13299–13313 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. King, Z. T. et al. Coro1B and Coro1C regulate lamellipodia dynamics and cell motility by tuning branched actin turnover. J. Cell Biol. https://doi.org/10.1083/jcb.202111126 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  197. Cai, L., Makhov, A. M., Schafer, D. A. & Bear, J. E. Coronin 1B antagonizes cortactin and remodels Arp2/3-containing actin branches in lamellipodia. Cell 134, 828–842 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Hakala, M. et al. Twinfilin uncaps filament barbed ends to promote turnover of lamellipodial actin networks. Nat. Cell Biol. 23, 147–159 (2021).

    Article  CAS  PubMed  Google Scholar 

  199. Shekhar, S., Hoeprich, G. J., Gelles, J. & Goode, B. L. Twinfilin bypasses assembly conditions and actin filament aging to drive barbed end depolymerization. J. Cell Biol. https://doi.org/10.1083/jcb.202006022 (2021).

    Article  PubMed  Google Scholar 

  200. Svitkina, T. M. & Borisy, G. G. Arp2/3 complex and actin depolymerizing factor/cofilin in dendritic organization and treadmilling of actin filament array in lamellipodia. J. Cell Biol. 145, 1009–1026 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Fehon, R. G., McClatchey, A. I. & Bretscher, A. Organizing the cell cortex: the role of ERM proteins. Nat. Rev. Mol. Cell Biol. 11, 276–287 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Gunning, P. W., Hardeman, E. C., Lappalainen, P. & Mulvihill, D. P. Tropomyosin — master regulator of actin filament function in the cytoskeleton. J. Cell Sci. 128, 2965–2974 (2015).

    CAS  PubMed  Google Scholar 

  203. Ghosh, A. & Fowler, V. M. Tropomodulins. Curr. Biol. 31, R501–R503 (2021).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank the following individuals for their valuable input: A. Akhtar, H. Aydin, L. Blanchoin, T. Bretscher, P. Chinnery, D. Colon-Ramos, J. Cooper, R. Dominguez, S. Eustermann, V. Fowler, J. Gautier, E. Gingmer, B. Goode, R. Grosse, A. Henn, R. Kay, L. Kiss, J. Kollman, M. Mietalobs, D. Mullins, M. Ostap, K. Pfanner, M. Picard, T. Pollard, L. Pon, M. Quinlan, K. Rottner, Y. Sancak, M. Schuldiner, B. Schulman, T. Schwarz, O. Shirihai, T. Svitkina, C. Thompson, C. Toseland, M. Vartiainen & B. Webb. During the revision process, the material related to many of these contributions was removed, but the correspondence is still valued. This work was supported by NIH grant R35 GM122545.

Author information

Author notes

  1. Tak Shun Fung

    Present address: Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

  2. Rajarshi Chakrabarti

    Present address: MitoCare Center, Department of Pathology and Genomic Medicine, Thomas Jefferson University, Philadelphia, PA, USA

Authors and Affiliations

  1. Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth College, Hanover, NH, USA

    Tak Shun Fung, Rajarshi Chakrabarti & Henry N. Higgs

Authors
  1. Tak Shun Fung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajarshi Chakrabarti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Henry N. Higgs
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors researched data for the article and contributed substantially to the discussion of content. H.N.H. wrote the article. T.S.F. prepared figures. All authors reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Henry N. Higgs.

Ethics declarations

Competing interests

The authors declare no competing financial or non-financial interests.

Peer review

Peer review information

Nature Reviews Molecular Cell Biology thanks Sirio Dupont, Pekka Lappalainen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fung, T.S., Chakrabarti, R. & Higgs, H.N. The multiple links between actin and mitochondria. Nat Rev Mol Cell Biol 24, 651–667 (2023). https://doi.org/10.1038/s41580-023-00613-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41580-023-00613-y

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing