生物
细胞生物学
线粒体
线粒体融合
内质网
细胞器
线粒体DNA
遗传学
基因
作者
Yujie Li,Dawei Huang,Jia Lu,Fugen Shangguan,Shiwei Gong,Linhua Lan,Zhiyin Song,Juan Xu,Chaojun Yan,Tongke Chen,Yizheng Tan,Yongzhang Liu,Xingxu Huang,Carolyn K. Suzuki,Zhongzhou Yang,Guanlin Yang,Bin Lü
出处
期刊:Research
[AAAS00]
日期:2023-01-01
卷期号:6
被引量:4
标识
DOI:10.34133/research.0175
摘要
Interorganelle contacts and communications are increasingly recognized to play a vital role in cellular function and homeostasis. In particular, the mitochondria-endoplasmic reticulum (ER) membrane contact site (MAM) is known to regulate ion and lipid transfer, as well as signaling and organelle dynamics. However, the regulatory mechanisms of MAM formation and their function are still elusive. Here, we identify mitochondrial Lon protease (LonP1), a highly conserved mitochondrial matrix protease, as a new MAM tethering protein. The removal of LonP1 substantially reduces MAM formation and causes mitochondrial fragmentation. Furthermore, deletion of LonP1 in the cardiomyocytes of mouse heart impairs MAM integrity and mitochondrial fusion and activates the unfolded protein response within the ER (UPRER). Consequently, cardiac-specific LonP1 deficiency causes aberrant metabolic reprogramming and pathological heart remodeling. These findings demonstrate that LonP1 is a novel MAM-localized protein orchestrating MAM integrity, mitochondrial dynamics, and UPRER, offering exciting new insights into the potential therapeutic strategy for heart failure.
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