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