@article {69420, title = {An interphase actin wave promotes mitochondrial content mixing and organelle homeostasis.}, journal = {Nat Commun}, volume = {15}, year = {2024}, month = {2024 May 07}, pages = {3793}, abstract = {

Across the cell cycle, mitochondrial dynamics are regulated by a cycling wave of actin polymerization/depolymerization. In metaphase, this wave induces actin comet tails on mitochondria that propel these organelles to drive spatial mixing, resulting in their equitable inheritance by daughter cells. In contrast, during interphase the cycling actin wave promotes localized mitochondrial fission. Here, we identify the F-actin nucleator/elongator FMNL1 as a positive regulator of the wave. FMNL1-depleted cells exhibit decreased mitochondrial polarization, decreased mitochondrial oxygen consumption, and increased production of reactive oxygen species. Accompanying these changes is a loss of hetero-fusion of wave-fragmented mitochondria. Thus, we propose that the interphase actin wave maintains mitochondrial homeostasis by promoting mitochondrial content mixing. Finally, we investigate the mechanistic basis for the observation that the wave drives mitochondrial motility in metaphase but mitochondrial fission in interphase. Our data indicate that when the force of actin polymerization is resisted by mitochondrial tethering to microtubules, as in interphase, fission results.

}, keywords = {Actins, Animals, Formins, Hela Cells, Homeostasis, Humans, Interphase, Microtubules, Mitochondria, Mitochondrial Dynamics, Mitochondrial Proteins, Reactive Oxygen Species}, issn = {2041-1723}, doi = {10.1038/s41467-024-48189-1}, author = {Coscia, Stephen M and Moore, Andrew S and Thompson, Cameron P and Tirrito, Christian F and Ostap, E Michael and Holzbaur, Erika L F} } @article {69400, title = {Mitochondrially-associated actin waves maintain organelle homeostasis and equitable inheritance.}, journal = {Curr Opin Cell Biol}, volume = {88}, year = {2024}, month = {2024 Apr 30}, pages = {102364}, abstract = {

First identified in dividing cells as revolving clusters of actin filaments, these are now understood as mitochondrially-associated actin waves that are active throughout the cell cycle. These waves are formed from the polymerization of actin onto a subset of mitochondria. Within minutes, this F-actin depolymerizes while newly formed actin filaments assemble onto neighboring mitochondria. In interphase, actin waves locally fragment the mitochondrial network, enhancing mitochondrial content mixing to maintain organelle homeostasis. In dividing cells actin waves spatially mix mitochondria in the mother cell to ensure equitable partitioning of these organelles between daughter cells. Progress has been made in understanding the consequences of actin cycling as well as the underlying molecular mechanisms, but many questions remain, and here we review these elements. Also, we draw parallels between mitochondrially-associated actin cycling and cortical actin waves. These dynamic systems highlight the remarkable plasticity of the actin cytoskeleton.

}, issn = {1879-0410}, doi = {10.1016/j.ceb.2024.102364}, author = {Coscia, Stephen M and Moore, Andrew S and Wong, Yvette C and Holzbaur, Erika L F} } @article {67177, title = {Actin cables and comet tails organize mitochondrial networks in mitosis.}, journal = {Nature}, volume = {591}, year = {2021}, month = {2021 Mar 03}, pages = {659-664}, abstract = {

Symmetric cell division requires the even partitioning of genetic information and cytoplasmic contents between daughter cells. Whereas the mechanisms coordinating the segregation of the genome are well known, the processes that ensure organelle segregation between daughter cells remain less well understood. Here we identify multiple actin assemblies with distinct but complementary roles in mitochondrial organization and inheritance in mitosis. First, we find a dense meshwork of subcortical actin cables assembled throughout the mitotic cytoplasm. This network scaffolds the endoplasmic reticulum and organizes three-dimensional mitochondrial positioning to ensure the equal segregation of mitochondrial mass at cytokinesis. Second, we identify a dynamic wave of actin filaments reversibly assembling on the surface of mitochondria during mitosis. Mitochondria sampled by this wave are enveloped within actin clouds that can spontaneously break symmetry to form elongated comet tails. Mitochondrial comet tails promote randomly directed bursts of movement that shuffle mitochondrial position within the mother cell to randomize inheritance of healthy and damaged mitochondria between daughter cells. Thus, parallel mechanisms mediated by the actin cytoskeleton ensure both equal and random inheritance of mitochondria in symmetrically dividing cells.

}, issn = {1476-4687}, doi = {10.1038/s41586-021-03309-5}, author = {Moore, Andrew S and Coscia, Stephen M and Simpson, Cory L and Ortega, Fabian E and Wait, Eric C and Heddleston, John M and Nirschl, Jeffrey J and Obara, Christopher J and Guedes-Dias, Pedro and Boecker, C Alexander and Chew, Teng-Leong and Theriot, Julie A and Lippincott-Schwartz, Jennifer and Holzbaur, Erika L F} }