Extreme Acetylation of the Cardiac Mitochondrial Proteome Does Not Promote Heart Failure.

ABSTRACT:

Rationale

Circumstantial evidence links the development of heart failure to posttranslational modifications of mitochondrial proteins, including lysine acetylation (Kac). Nonetheless, direct evidence that Kac compromises mitochondrial performance remains sparse.

Objective

This study sought to explore the premise that mitochondrial Kac contributes to heart failure by disrupting oxidative metabolism.

Methods and results

A DKO (dual knockout) mouse line with deficiencies in CrAT (carnitine acetyltransferase) and Sirt3 (sirtuin 3)-enzymes that oppose Kac by buffering the acetyl group pool and catalyzing lysine deacetylation, respectively-was developed to model extreme mitochondrial Kac in cardiac muscle, as confirmed by quantitative acetyl-proteomics. The resulting impact

SUBMITTER: Davidson MT 

PROVIDER: S-EPMC9161399 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature