Increased Drp1 Acetylation by Lipid Overload Induces Cardiomyocyte Death and Heart Dysfunction
This week we profile a recent publication in Circulation Research from the laboratory of Dr. Wang Wang (pictured, center) at UW.
Can you provide a brief overview of your lab’s current research focus?
The Wang lab uses molecular and cellular biology, high resolution imaging, and genetic animal models to study the role of mitochondrial function and energy metabolism in the development of heart disease.
What is the significance of the findings in this publication?
Metabolic syndrome, including obesity and insulin resistance, compromises energy metabolism, mitochondrial function and heart performance. Here, we used animal and cell culture models in rodents or monkeys and found that lipid overload decreased NAD+ levels and increased the acetylation of a fission protein Drp1 at K642. This mechanism promotes Drp1 activation, mitochondrial translocation, VDAC1 binding, and eventually mitochondrial fission and heart cell dysfunction. These findings provide new information regarding how lipid overload regulates redox environment, protein acetylation, and the function of mitochondrial fission protein Drp1 in the heart.
What are the next steps for this research?
Currently, we are further elucidating the mechanisms by which K642 acetylation regulates Drp1 activity, how Drp1 interacts with VDAC1 in heart cells, and whether manipulating Drp1 acetylation at this site can protect the heart from lipid overload-induced dysfunction in vivo.