Interaction of mitochondrial fission factor with dynamin related protein 1 governs physiological mitochondrial function in vivo.

ABSTRACT: Mitochondria form a dynamic network governed by a balance between opposing fission and fusion processes. Because excessive mitochondrial fission correlates with numerous pathologies, including neurodegeneration, the mechanism governing fission has become an attractive therapeutic strategy. However, targeting fission is a double-edged sword as physiological fission is necessary for mitochondrial function. Fission is trigged by Drp1 anchoring to adaptors tethered to the outer mitochondrial membrane. We designed peptide P259 that distinguishes physiological from pathological fission by specifically inhibiting Drp1's interaction with the Mff adaptor. Treatment of cells with P259 elongated mitochondria and disrupted mitochondrial function and motility. Sustained in vivo treatment caused a decli

SUBMITTER: Kornfeld OS 

PROVIDER: S-EPMC6145916 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature