Actin cables and comet tails organize mitochondrial networks in mitosis

Abstract

Symmetric cell division requires the even partitioning of genetic information and cytoplasmic contents between daughter cells. While the mechanisms coordinating the segregation of the genome are well known, the processes which ensure organelle segregation between daughter cells remain less well-understood 1 . Here, we identify multiple actin assemblies that play 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 through 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.

The need for high-quality oocyte mitochondria at extreme ploidy dictates mammalian germline development

“…The zygote is assumed to have around half a million copies of mitochondrial DNA (exact number 2 19 ), which are randomly partitioned to the daughter cells at each cell division. The pattern of segregation is in agreement with recent evidence for actin-mediated mixing of mitochondria within cells during mitosis leading to random segregation ( Moore et al, 2021 ). We assume independent segregation of mitochondria with one mtDNA per mitochondrion, and do not consider complications that might arise from the packaging of multiple mtDNA copies per mitochondrion ( Floros et al, 2018 ).…”

“…The extreme ploidy in the zygote allows early rounds of cell division to occur without mitochondrial replication, and hence without de novo mutational input. These initial cell divisions generate little between-cell differences, as segregational variance is weak when numbers are high and mitochondria segregate randomly during mitosis [52] (e.g. Follicular atresia is another female germline feature examined in our modelling, in which there is over-proliferation of PGCs followed by ~80% loss early in development, before oocyte maturation [31,39].…”

“…The extreme ploidy in the zygote allows early rounds of cell division to occur without mitochondrial replication, and hence without de novo mutational input. These initial cell divisions generate little between-cell differences, as segregational variance is weak when numbers are high and mitochondria segregate randomly during mitosis ( Moore et al, 2021 ) (e.g. Figure 1B before PGC specification).…”

Self-DNA Sensing by cGAS-STING and TLR9 in Autoimmunity: Is the Cytoskeleton in Control?

“…Transient actin polymerization induced by Arp2/3, cortactin, and formins contributes to mitochondria fission and conversely, actin relaxation allows mitochondria fusion (82,83). In addition, actin flows were recently shown to ensure mitochondria redistribution to daughter cells during mitosis (84), ensuring a proper metabolic balance and mitochondrial turnover. Importantly, mitochondrial disposal by mitophagy is mediated by Arp2/3-dependent actin polymerization downstream of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ) (85).…”

Mitochondrial Protein Abundance Gradients Require the Distribution of Separated Mitochondria

“…Using confocal microscopy, we next investigated the cell cycle stages at which the inner-cellular mitochondrial protein abundance gradients are established. Upon cell division, the mitochondrial tubules undergo a massive structural rearrangement involving fragmentation, condensation, and mixing of the network [21][22][23][24]. These morphological changes may influence the analysis of the gradients despite the optical sectioning provided by the confocal microscope, as two axially overlapping mitochondria might add up their fluorescence signals.…”