Mitotic Phosphorylation of Dynamin-related GTPase Drp1 Participates in Mitochondrial Fission

Abstract

Organelles are inherited to daughter cells beyond dynamic changes of the membrane structure during mitosis. Mitochondria are dynamic entities, frequently dividing and fusing with each other, during which dynamin-related GTPase Drp1 is required for the fission reaction. In this study, we analyzed mitochondrial dynamics in mitotic mammalian cells. Although mitochondria in interphase HeLa cells are long tubular network structures, they are fragmented in early mitotic phase, and the filamentous network structures are subsequently reformed in the daughter cells. In marked contrast, tubular mitochondrial structures are maintained during mitosis in Drp1 knockdown cells, indicating that the mitochondrial fragmentation in mitosis requires mitochondrial fission by Drp1. Drp1 was specifically phosphorylated in mitosis by Cdk1/cyclin B on Ser-585. Exogenous expression of unphosphorylated mutant Drp1 S585A led to reduced mitotic mitochondrial fragmentation. These results suggest that phosphorylation of Drp1 on Ser-585 promotes mitochondrial fission in mitotic cells.

Quality control of mitochondria during aging: Is there a good and a bad side of mitochondrial dynamics?

“…Progression from G1 to S phase during the cell cycle was shown to depend on hyperfusion of mitochondria. Also, mitochondrial fission was increased during mitosis [60][61][62]. These results further strengthen the general view that mitochondrial dynamics is strictly regulated at several levels (for a review see [63]).…”

Mitochondrial respiratory chain dysfunction: Implications in neurodegeneration

“…Despite the overall decrease in Drp1 levels found in AD brains, the Drp1 fraction associated to mitochondria was not altered, suggesting that enough Drp1 is traslocated to mitochondria to induce fission ). In addition, higher levels of phosphorylated and nitrosylated Drp1 were found in AD brains compared with control brains Cho et al, 2009), together with post-translational modifications associated to enhanced mitochondrial fission activity that, interestingly, can be induced by Aβ (Taguchi et al, 2007;Cho et al, 2009). Finally, Drp1 was reported to interact and colocalize with Aβ monomers and oligomers in human and mice AD brains, interactions that increase with disease progression , thus supporting a direct role of Aβ on Drp1 pathological modifications.…”

The mitochondrial dynamics in cancer and immune-surveillance

“…Mitochondrial fission is important for various cellular processes, such as mitochondrial clearance through mitophagy [19], ROS production [20], regulation of cell proliferation [21][22][23] and apoptosis [24,25]. The main protein driving mitochondrial fragmentation is the GTPase Dynamin-Related-Protein-1 (Drp1) [26].…”