Cyclin C directly stimulates Drp1 GTP affinity to mediate stress-induced mitochondrial hyperfission.

ABSTRACT: Mitochondria exist in an equilibrium between fragmented and fused states that shifts heavily toward fission in response to cellular damage. Nuclear-to-cytoplasmic cyclin C relocalization is essential for dynamin-related protein 1 (Drp1)-dependent mitochondrial fission in response to oxidative stress. This study finds that cyclin C directly interacts with the Drp1 GTPase domain, increases its affinity to GTP, and stimulates GTPase activity in vitro. In addition, the cyclin C domain that binds Drp1 is contained within the non-Cdk binding second cyclin box domain common to all cyclin family members. This interaction is important, as this domain is sufficient to induce mitochondrial fission when expressed in mouse embryonic fibroblasts in the absence of additional stress signals. Using gel fil

SUBMITTER: Ganesan V 

PROVIDER: S-EPMC6589575 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature