Interplay between O‐GlcNAc and acetylation regulates mitochondrial function (756.7)

• DOI: 10.1096/fasebj.28.1_supplement.756.7
• Publication Date: 2021-06-15T17:18:20Z
• Authors: Ee Phie Tan; Christopher Lanza; Russell Swerdlow; Chad Slawson
• Keywords: 0303 health sciences; 03 medical and health sciences

O‐linked N‐acetylglucosamine (O‐GlcNAc) is a post‐translational modification involving an attachment of a single N‐acetylglucosamine residue to serine or threonine residues in nuclear and cytoplasmic proteins. The O‐GlcNAc modification is processed by O‐GlcNAc transferase (OGT), which adds the modification to the protein and O‐GlcNAcase (OGA), which removes it. Recent evident links the regulation of mitochondrial function to O‐GlcNAcylation. For example, we used a quantitative proteomics screen to determine that an OGT or OGA gain of function altered mitochondrial protein expression including proteins involved in the respiratory chain and TCA cycle. Furthermore, mitochondrial morphology and both cellular respiration and glycolysis were altered in these cells. Potentially, altered O‐GlcNAc is changing the levels of mitochondria acetylation. Acetylation is a common post‐translational modification that regulates proteins function. The objective of our study is to investigate if O‐GlcNAc is regulating the acetylation of mitochondrial proteins. Herein, we demonstrate that alterations to the cellular levels of O‐GlcNAc changes mitochondrial acetylation as well as the expression of SIRT3. These data demonstrate that alterations to the cellular homeostasis of O‐GlcNAc levels may have a profound effect on the mitochondrial acetylation.Grant Funding Source: P30AG035982