| First Author | Thapa D | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 10665 |
| PubMed ID | 32606301 | Mgi Jnum | J:295924 |
| Mgi Id | MGI:6451972 | Doi | 10.1038/s41598-020-67812-x |
| Citation | Thapa D, et al. (2020) Cardiomyocyte-specific deletion of GCN5L1 in mice restricts mitochondrial protein hyperacetylation in response to a high fat diet. Sci Rep 10(1):10665 |
| abstractText | Mitochondrial lysine acetylation regulates several metabolic pathways in cardiac cells. The current study investigated whether GCN5L1-mediated lysine acetylation regulates cardiac mitochondrial metabolic proteins in response to a high fat diet (HFD). GCN5L1 cardiac-specific knockout (cKO) mice showed significantly reduced mitochondrial protein acetylation following a HFD relative to wildtype (WT) mice. GCN5L1 cKO mice did not display any decrease in ex vivo cardiac workload in response to a HFD. In contrast, ex vivo cardiac function in HFD-fed WT mice dropped ~ 50% relative to low fat diet (LFD) fed controls. The acetylation status of electron transport chain Complex I protein NDUFB8 was significantly increased in WT mice fed a HFD, but remained unchanged in GCN5L1 cKO mice relative to LFD controls. Finally, we observed that inhibitory acetylation of superoxide dismutase 2 (SOD2) at K122 was increased in WT (but not cKO mice) on a HFD. This correlated with significantly increased cardiac lipid peroxidation in HFD-fed WT mice relative to GCN5L1 cKO animals under the same conditions. We conclude that increased GCN5L1 expression in response to a HFD promotes increased lysine acetylation, and that this may play a role in the development of reactive oxygen species (ROS) damage caused by nutrient excess. |
