Increased Drp1 acetylation by lipid overload induces cardiomyocyte death and heart dysfunction

Despite the increasing prevalence of heart complications in obese and diabetic patients, our knowledge on how obese and diabetes mellitus impair heart function is very limited.

In this study, we used animal and cell culture models in rodents or monkeys and generated lipid overload models to mimic obesity conditions. We found that excessive lipid supply decreased nicotinamide adenine dinucleotide (oxidized) levels and increased the acetylation of a fission protein Drp1 at a specific lysine residue (K642). Drp1 acetylation at K642 activated Drp1 through phosphorylation, mitochondrial translocation, and oligomerization.