Lon in maintaining mitochondrial and endoplasmic reticulum homeostasis
As a vital member of AAA+ (ATPase associated with diverse cellular activities) protein superfamily, Lon, a homo-hexameric ring-shaped protein complex with a serine–lysine catalytic dyad, is highly conserved throughout almost all prokaryotic and eukaryotic organisms. Lon protease (LONP) plays an important role in maintaining mitoproteostasis through selectively recognizing and degrading oxidatively modified mitoproteins within mitochondrial matrix, such as oxidized aconitase, phosphorylated mitochondrial transcription factor A, etc. Furthermore, the up-regulated LONP increased mitochondrial ROS generation to promote cell survival, cell proliferation, epithelial–mesenchymal transition, and cell migration, which was attributed to the up-regulation of NADH:ubiquinone oxidoreductase core subunit S8 via interaction with chaperone Lon under hypoxic or oxidative stress in tumorigenesis. In addition, Lon also participated in protein kinase RNA (PKR)-like endoplasmic reticulum kinase signaling pathway under endoplasmic reticulum (ER) stress. In short, Lon, as a pivotal stress-responsive protein that involved in the crosstalks among mitochondria, ER and nucleus, participated in multifarious important cellular processes crucial for cell survival, such as the mitochondrial protein quality control system, the mitochondrial unfolded protein response, the mtDNA maintenance, and the ER unfolded protein response.
KeywordsLon Mitochondrial protein quality control Mitochondrial unfolded protein response mtDNA maintenance Endoplasmic reticulum unfolded protein response Chaperone
This work was supported by the District Program of National Natural Science Foundation of China (31460426), the Youth Program of National Natural Science Foundation of China (31601577), the Excellent Youth Talents of Zunyi Medical University (17zy-006), the cooperation projects of the Science and Technology Department of Guizhou Province (LH7546), the projects of Zunyi Science and Technology Bureau (201718), the projects of Zunyi Medical University (ZMKD2013-022) and the supporting discipline construction fund of Zunyi Medical University Ph.D. authorization.
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Conflict of interest
All authors declare that there are no conflicts of interest.
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