Description
Cycling clouds of actin filaments regulate mitochondria size and distribution in mitotic cells
Moore, A.S., Coscia, S.M., Simpson, C.S., Nirschl, J.J., and Holzbaur, E.L.F.
Perelman School of Medicine, University of Pennsylvania
In mammalian cells, mitochondria form interconnected networks that fragment prior to cell division to allow for segregation of mitochondrial mass between daughter cells. Equitable partitioning of mitochondria is critically important to prevent bottleneck effects and the potential expansion of deleterious mitochondrial DNA mutations. To date, the precise mechanism regulating mitochondria inheritance remains controversial. Previous work from our lab identified a dynamic, rotating cloud of actin filaments propagating through interphase mitochondrial networks at a rate of ~5µm/min. We observed that actin clouds move in a step-wise manner, cycling onto and off of subpopulations of mitochondria, transiently inducing fission. Here, using HeLa cells and primary epidermal keratinocytes, we find that mitochondrial actin clouds persist through all stages of the cell cycle, but are markedly upregulated at the G2/M transition. Specifically, we observe that metaphase actin clouds more than double in size and velocity, and display a stronger bias for persistent, unidirectional motility as compared to interphase clouds. Cycling is dependent on CDK1, as inhibition of the mitotic kinase robustly blocks actin cloud formation, and enhanced cycling correlates with increased CDK1 activity during mitosis. We observe that rapidly transiting mitotic actin clouds have profound effects on mitochondrial networks. In prometaphase, actin clouds promote and maintain mitochondrial fragmentation. In metaphase cells, cycling actin filaments induce microtubule-independent motility of mitochondria, which ensures homogenous distribution of mitochondria throughout the cell. In telophase, we observe selective actin assembly on mitochondria localized to the cleavage furrow. Based on these observations, we hypothesize that mitochondrial actin clouds function as a mechanism to fragment and symmetrically partition mitochondria between daughter cells during cell division.