Dong 2024 Nat Commun

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Dong J, Chen L, Ye F, Tang J, Liu B, Lin J, Zhou PH, Lu B, Wu M, Lu JH, He JJ, Engelender S, Meng Q, Song Z, He H (2024) Mic19 depletion impairs endoplasmic reticulum-mitochondrial contacts and mitochondrial lipid metabolism and triggers liver disease.

Β» Nat Commun 15:168. PMID: 38168065 Open Access

Dong Jun, Chen Li, Ye Fei, Tang Junhui, Liu Bing, Lin Jiacheng, Zhou Pang-Hu, Lu Bin, Wu Min, Lu Jia-Hong, He Jing-Jing, Engelender Simone, Meng Qingtao, Song Zhiyin, He He (2024) Nat Commun

Abstract: Endoplasmic reticulum (ER)-mitochondria contacts are critical for the regulation of lipid transport, synthesis, and metabolism. However, the molecular mechanism and physiological function of endoplasmic reticulum-mitochondrial contacts remain unclear. Here, we show that Mic19, a key subunit of MICOS (mitochondrial contact site and cristae organizing system) complex, regulates ER-mitochondria contacts by the EMC2-SLC25A46-Mic19 axis. Mic19 liver specific knockout (LKO) leads to the reduction of ER-mitochondrial contacts, mitochondrial lipid metabolism disorder, disorganization of mitochondrial cristae and mitochondrial unfolded protein stress response in mouse hepatocytes, impairing liver mitochondrial fatty acid Ξ²-oxidation and lipid metabolism, which may spontaneously trigger nonalcoholic steatohepatitis (NASH) and liver fibrosis in mice. Whereas, the re-expression of Mic19 in Mic19 LKO hepatocytes blocks the development of liver disease in mice. In addition, Mic19 overexpression suppresses MCD-induced fatty liver disease. Thus, our findings uncover the EMC2-SLC25A46-Mic19 axis as a pathway regulating ER-mitochondria contacts, and reveal that impairment of ER-mitochondria contacts may be a mechanism associated with the development of NASH and liver fibrosis.

β€’ Bioblast editor: Plangger M

Labels: MiParea: Respiration, Genetic knockout;overexpression 

Organism: Mouse  Tissue;cell: Liver  Preparation: Homogenate 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS  HRR: Oxygraph-2k 

2024-01, CN 

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