Mitochondria Localize to the Cleavage Furrow in Mammalian Cytokinesis

Abstract

Mitochondria are dynamic organelles with multiple cellular functions, including ATP production, calcium buffering, and lipid biosynthesis. Several studies have shown that mitochondrial positioning is regulated by the cytoskeleton during cell division in several eukaryotic systems. However, the distribution of mitochondria during mammalian cytokinesis and whether the distribution is regulated by the cytoskeleton has not been examined. Using live spinning disk confocal microscopy and quantitative analysis of mitochondrial fluorescence intensity, we demonstrate that mitochondria are recruited to the cleavage furrow during cytokinesis in HeLa cells. After anaphase onset, the mitochondria are recruited towards the site of cleavage furrow formation, where they remain enriched as the furrow ingresses and until cytokinesis completion. Furthermore, we show that recruitment of mitochondria to the furrow occurs in multiple mammalian cells lines as well as in monopolar, bipolar, and multipolar divisions, suggesting that the mechanism of recruitment is conserved and robust. Using inhibitors of cytoskeleton dynamics, we show that the microtubule cytoskeleton, but not actin, is required to transport mitochondria to the cleavage furrow. Thus, mitochondria are specifically recruited to the cleavage furrow in a microtubule-dependent manner during mammalian cytokinesis. Two possible reasons for this could be to localize mitochondrial function to the furrow to facilitate cytokinesis and / or ensure accurate mitochondrial inheritance.

Myo19 Ensures Symmetric Partitioning of Mitochondria and Coupling of Mitochondrial Segregation to Cell Division

“…RAL-induced fission of mitochondria in mitosis has very recently been proposed to contribute to their partitioning at cell division [36]. Although a recent paper [37] reported that mitochondria were recruited to the cleavage furrow during cytokinesis in HeLa and other cell types, a process its authors concluded was dependent on microtubules but not actin, we never observed this in our experiments (see, for example, Figures 3 and 4A; Figures S3A and S3D; Movie S1). …”

Dynamics of the mitochondrial network during mitosis

“…Indeed, while mitochondria congress towards the division plane from anaphase to early cytokinesis, presumably to deliver ATP for the contraction of the actomyosin ring [5], in late cytokinesis/early G 1 , mitochondria are transported away from the division plane and spread towards the periphery of the two daughter cells [4]. This latter phenomenon is dependent on Miro's interaction with a cell-cycle-specific cytoskeletal adaptor, the centromeric protein F (Cenp-F).…”

“…Thus steering mitochondria close to ATP demanding sites during mitosis (e.g. the actomyosin ring [5]) might be physiologically relevant.…”

“…In interphase cells, the mitochondria are arranged in elongated tubules whereas in mitosis, the network is fragmented ( Figure 1B). At the exit of mitosis and initiation of cytokinesis, the mitochondria tubules merge again to reform an interconnected network [3] that is distributed across the cell [4,5].…”

Phosphorylation-Induced Motor Shedding Is Required at Mitosis for Proper Distribution and Passive Inheritance of Mitochondria

“…However, for passive inheritance to occur, mitochondria must also release from cytoskeletal anchors and distribute evenly throughout the cytoplasm, which fragmentation alone does not guarantee (Mishra and Chan, 2014). Conflicting reports have implicated microtubules and actin as active drivers of mitochondrial inheritance, but it remains unknown how these elements would position mitochondria during cell division (Lawrence and Mandato, 2013c; Lee et al, 2007; Rohn et al, 2014). …”