The acetylation of MDH1 and IDH1 is associated with energy metabolism in acute liver failure

Chunxia Shi; Yanqiong Zhang; Qian Chen; Yukun Wang; Danmei Zhang; Jin Guo; Qingqi Zhang; Wenbin Zhang; Zuojiong Gong

doi:10.1016/j.isci.2024.109678

The acetylation of MDH1 and IDH1 is associated with energy metabolism in acute liver failure

iScience. 2024 Apr 6;27(5):109678. doi: 10.1016/j.isci.2024.109678. eCollection 2024 May 17.

Authors

Chunxia Shi¹, Yanqiong Zhang¹, Qian Chen², Yukun Wang¹, Danmei Zhang¹, Jin Guo¹, Qingqi Zhang¹, Wenbin Zhang³, Zuojiong Gong¹

Affiliations

¹ Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan 430060, China.
² Department of Cardiology, Wuhan No.1 Hospital, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan 430022, China.
³ Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, China.

Abstract

The liver is the main organ associated with metabolism. In our previous studies, we identified that the metabolic enzymes malate dehydrogenase 1 (MDH1) and isocitrate dehydrogenase 1 (IDH1) were differentially expressed in ALF. The aim of this study was to explore the changes in the acetylation of MDH1 and IDH1 and the therapeutic effect of histone deacetylase (HDAC) inhibitor in acute liver failure (ALF). Decreased levels of many metabolites were observed in ALF patients. MDH1 and IDH1 were decreased in the livers of ALF patients. The HDAC inhibitor ACY1215 improved the expression of MDH1 and IDH1 after treatment with MDH1-siRNA and IDH1-siRNA. Transfection with mutant plasmids and adeno-associated viruses, identified MDH1 K118 acetylation and IDH1 K93 acetylation as two important sites that regulate metabolism in vitro and in vivo.

Keywords: Hepatology; Human metabolism; Molecular biology.