Protein acetylation is a highly abundant post-translational modification in the mitochondria. Changes in cellular nutrient availability or energy status induce global changes in mitochondrial protein acetylation. Over one-third of all proteins in the mitochondria are acetylated, of which the majority are involved in some aspect of energy metabolism. Mitochondrial protein acetylation levels are primarily regulated by sirtuin 3 (SIRT3), a member of the sirtuin family of NAD+-dependent protein deacetylases. We identified an important regulatory role for SIRT3 as a key modulator of energy homeostasis. In the absence of SIRT3, mitochondrial proteins become hyperacetylated, have altered function, and lead to mitochondrial dysfunction. We are currently studying acetylated mitochondrial proteins, their regulation by SIRT3, and further defining the role of protein acetylation in mitochondrial function. Read More...

In an extension from the above project, our laboratory is exploring the regulatory role for novel post-translational modifications. We are working to identify mitochondrial proteins that are modified, their regulation, and further defining nutrient integration and signaling into mitochondrial function. Read More...

Mitochondrial dysfunction is correlated with several types of cancer. However, mitochondria perform several additional functions, including synthesis, degradation, fission/fusion, and signaling. Thus, before we can understand how mitochondrial dysfunction contributes to cancer development, we need to better understand mitochondrial function. Our overall objective is to better understand the interaction between mitochondrial genes and function, and specifically which pathways are dysfunctional in cancers. Read More...