biostudies-literatureCoscia SMU.S. Department of Health & Human Services | NIH | National Institute of General Medical SciencesNIGMS NIH HHS3793https://www.ebi.ac.uk/biostudies/studies/S-EPMC11076292biostudies-literatureUnknown15(1)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 miNature communicationsAn interphase actin wave promotes mitochondrial content mixing and organelle homeostasis.PMC11076292R35 GM126950RM1 GM136511Holzbaur ELFCoscia SMThompson CPOstap EMTirrito CFMoore ASfalseAn interphase actin wave promotes mitochondrial content mixing and organelle homeostasis.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 mi2024-01-01T00:00:00Z2024 May2026-06-01T19:58:02.074Z2026-05-20T03:07:52.644ZS-EPMC110762923871482210.1038/s41467-024-48189-1