AKAP1 Protects from Cerebral Ischemic Stroke by Inhibiting Drp1-Dependent Mitochondrial Fission.

ABSTRACT: Mitochondrial fission and fusion impact numerous cellular functions and neurons are particularly sensitive to perturbations in mitochondrial dynamics. Here we describe that male mice lacking the mitochondrial A-kinase anchoring protein 1 (AKAP1) exhibit increased sensitivity in the transient middle cerebral artery occlusion model of focal ischemia. At the ultrastructural level, AKAP1^-/- mice have smaller mitochondria and increased contacts between mitochondria and the endoplasmic reticulum in the brain. Mechanistically, deletion of AKAP1 dysregulates complex II of the electron transport chain, increases superoxide production, and impairs Ca²⁺ homeostasis in neurons subjected to excitotoxic glutamate. Ca²⁺ deregulation in neurons lacking AKAP1 can be attribu

SUBMITTER: Flippo KH 

PROVIDER: S-EPMC6146498 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature