AMPKα2 Protects Against the Development of Heart Failure by Enhancing Mitophagy via PINK1 Phosphorylation.

ABSTRACT:

Rationale

Mitochondrial dysfunction plays an important role in heart failure (HF). However, the molecular mechanisms regulating mitochondrial functions via selective mitochondrial autophagy (mitophagy) are poorly understood.

Objective

We sought to determine the role of AMPK (AMP-activated protein kinase) in selective mitophagy during HF.

Methods and results

An isoform shift from AMPKα2 to AMPKα1 was observed in failing heart samples from HF patients and transverse aortic constriction-induced mice, accompanied by decreased mitophagy and mitochondrial function. The recombinant adeno-associated virus Serotype 9-mediated overexpression of AMPKα2 in mouse hearts prevented the development of transverse aortic constriction-induced chronic HF by increasing mitophagy and impro

SUBMITTER: Wang B 

PROVIDER: S-EPMC5834386 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature