Mitochondrial MOF regulates energy metabolism in heart failure via ATP5B hyperacetylation
Year: 2024
Type: article
Abstract: Lysine acetylation is a conserved post-translational modification involved in energy metabolism in mitochondria and heart function. This study investigates the role of mitochondria-localized lysine acetyltransferase MOF (males absent on the first) in heart failure (HF). We find that MOF is upregulated in mitochondria during HF, and overexpression of mitochondria-targeted MOF (mtMOF) in mouse models results in mitochondria dysfunction, cardiac remodeling, and HF. Furthermore, sirtuin 3 (SIRT3) knockout aggravates mtMOF-induced damages, underscoring the role of MOF-catalyzed hyperacetylation in HF. Quantitative lysine acetylome analysis identifies ATP5B as a substrate of MOF. We demonstrate that the acetylation of ATP5B at K201, co-regulated by MOF and SIRT3, impairs mitochondrial respiration and energy metabolism both in vitro and in vivo. These findings suggest that the role of MOF in HF could be attributed to its regulation of ATP5B acetylation. Overall, our results highlight the disruptive impact of mitochondrial MOF on cardiac function and emphasize the significance of enzyme-catalyzed acetylation in mitochondria.
Source: Cell Reports
Authors: Yuehuai Hu, Yongjia Zheng, Cui Liu, Yuyu You, Ying Wu, Panxia Wang, Yiyang Wu, Hongjun Ba, Jing Lu, Yanqiu Yuan, Peiqing Liu, Yang Mao
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,460
Funders: National Natural Science Foundation of China, Sun Yat-sen University, Ministry of Science and Technology of the People's Republic of China, Guangdong Provincial Pearl River Talents Program, National Key Research and Development Program of China, Key Technologies Research and Development Program of Guangzhou, National Key New Drug Creation and Manufacturing Program, Ministry of Science and Technology
OpenAlex ID: W4403299520