Peridroplet mitochondria are associated with the severity of MASLD and the prevention of MASLD by diethyldithiocarbamate.

Autor:	Sun X; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Hepatology, State Key Lab of Digestive Health, Beijing, China., Yu Q; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Hepatology, State Key Lab of Digestive Health, Beijing, China., Qi Y; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Hepatology, State Key Lab of Digestive Health, Beijing, China., Kang B; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Hepatology, State Key Lab of Digestive Health, Beijing, China., Zhao X; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Hepatology, State Key Lab of Digestive Health, Beijing, China; Department of Hepatology, National Clinical Research Center for Digestive Diseases, Beijing, China; Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing, China., Liu L; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Hepatology, State Key Lab of Digestive Health, Beijing, China; Department of Hepatology, National Clinical Research Center for Digestive Diseases, Beijing, China; Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing, China., Wang P; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Hepatology, State Key Lab of Digestive Health, Beijing, China; Department of Hepatology, National Clinical Research Center for Digestive Diseases, Beijing, China; Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing, China., Cong M; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Hepatology, State Key Lab of Digestive Health, Beijing, China; Department of Hepatology, National Clinical Research Center for Digestive Diseases, Beijing, China; Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing, China., Liu T; Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Hepatology, State Key Lab of Digestive Health, Beijing, China; Department of Hepatology, National Clinical Research Center for Digestive Diseases, Beijing, China; Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing, China. Electronic address: liu_tianhui@mail.ccmu.edu.cn.
Jazyk:	angličtina
Zdroj:	Journal of lipid research [J Lipid Res] 2024 Aug; Vol. 65 (8), pp. 100590. Date of Electronic Publication: 2024 Jul 07.
DOI:	10.1016/j.jlr.2024.100590
Abstrakt:	Mitochondria can contact lipid droplets (LDs) to form peridroplet mitochondria (PDM) which trap fatty acids in LDs by providing ATP for triglyceride synthesis and prevent lipotoxicity. However, the role of PDM in metabolic dysfunction associated steatotic liver disease (MASLD) is not clear. Here, the features of PDM in dietary MASLD models with different severity in mice were explored. Electron microscope photographs show that LDs and mitochondria rarely come into contact with each other in normal liver. In mice fed with high-fat diet, PDM can be observed in the liver as early as the beginning of steatosis in hepatocytes. For the first time, we show that PDM in mouse liver varies with the severity of MASLD. PDM and cytosolic mitochondria were isolated from the liver tissue of MASLD and analyzed by quantitative proteomics. Compared with cytosolic mitochondria, PDM have enhanced mitochondrial respiration and ATP synthesis. Diethyldithiocarbamate (DDC) alleviates choline-deficient, L-amino acid-defined diet-induced MASLD, while increases PDM in the liver. Similarly, DDC promotes the contact of mitochondria-LDs in steatotic C3A cells in vitro. Meanwhile, DDC promotes triglyceride synthesis and improves mitochondrial dysfunction in MASLD. In addition, DDC upregulates perilipin 5 both in vivo and in vitro, which is considered as a key regulator in PDM formation. Knockout of perilipin 5 inhibits the contact of mitochondria-LDs induced by DDC in C3A cells. These results demonstrate that PDM might be associated with the progression of MASLD and the prevention of MASLD by DDC. Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu