An interphase actin wave promotes mitochondrial content mixing and 2 organelle homeostasis

ABSTRACT: Across the cell cycle, mitochondrial dynamics are regulated by a cycling wave of actin polymerization/depolymerization. In metaphase, this wave induces the assembly of actin comet tails on mitochondria that propel these organelles to drive spatial mixing,resulting in their equitable inheritance by daughter cells. In contrast, during interphasethe cycling actin wave promotes localized mitochondrial fission. Here, we identify the F-actin nucleator/elongator FMNL1 as a positive regulator of the wave. Depletion of FMNL1 ablates the actin wave, allowing us to assess the functional consequences in interphase cells. 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 investigated 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, fission results. In striking contrast, upon microtubule depolymerization actin wave-enveloped mitochondria in interphase cells display comet tail motility characteristic of metaphase cells, which are devoid of microtubule-mitochondria interactions, suggesting that microtubule tethering inhibits comet tail-driven motility.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Hossein Fazelinia  

LAB HEAD: Erika L.F. Holzbaur, Ph.D.

PROVIDER: PXD050085 | Pride | 2024-06-23

REPOSITORIES: Pride