Dong 2024 Nat Commun
| 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. https://doi.org/10.1038/s41467-023-44057-6 |
Β» Nat Commun 15:168. PMID: 38168065 Open Access
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) 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
HRR: Oxygraph-2k
2024-01
