Review Article

The Phosphorylation-Dependent Regulation of Mitochondrial Proteins in Stress Responses

Figure 1

Mitochondrial fission and fusion. (a) Mitochondrial fission is driven by Drp1. Drp1 is recruited to the mitochondrial outer membrane at the fission sites and promotes mitochondrial fission. Fis1 resides on the mitochondrial outer membrane and is considered to function as a receptor for Drp1. (b) Fusion is driven by OPA1 and mitofusins. Interactions between these proteins tether two adjacent mitochondria. Mitofusins mediate mitochondrial outer membrane fusion, while Opa1 mediates mitochondrial inner membrane fusion. (c) The mitochondrial fission-promoting activity of Drp1 is controlled by the phosphorylation of Drp1 at Ser637. PKA phosphorylates Drp1 and inhibits the translocation of Drp1 to mitochondrial fission sites. Conversely, the calcineurin-mediated dephosphorylation of Drp1 results in the recruitment of Drp1 to the mitochondria and promotes mitochondrial fission. AKAP121 is a mitochondria-localized adaptor protein that regulates mitochondrial dynamics by facilitating Drp1 phosphorylation via PKA anchoring on mitochondria. Siah2 promotes the degradation of AKAP121, which decreases Drp1 phosphorylation, thus resulting in mitochondrial fission.
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