title: The activation of protein homeostasis protective mechanisms perhaps is not responsible for lifespan extension caused by deficiencies of mitochondrial proteins in C. elegans.
abstract: During aging the ability of organisms to maintain the protein homeostasis declines and damaged and misfolded proteins accumulate in cells. But whether the deterioration of protein homeostasis is the cause or consequence of aging is not clearly understood. Mitochondrial dysfunctions usually lead to increased longevity in Caenorhabditis elegans, the cause of which is believed to be the activation of protein homeostasis protective mechanisms including mitochondrial unfolded protein response (UPR(mt)) and GCN-2 kinase mediated nutrient-sensing pathway. However, we investigated four genes which encode well-defined mitochondrial proteins and found that: (i) UPR(mt) activation was associated with not only increased longevity by knockdown of mfn-1, cco-1, or nuo-6, but also decreased longevity by mev-1 RNAi; (ii) The blockage of UPR(mt) pathway did not repress mfn-1, cco-1, or nuo-6 RNAi induced lifespan extension; (iii) The activation of UPR(mt) did not increase longevity; (iv) Knockdown of mfn-1, cco-1, or nuo-6 increased longevity independently of GCN-2. The combined results indicate that two important kinds of the protein homeostasis protective mechanisms, namely UPR(mt) and GCN-2 pathways, are not responsible for mitochondrial deficiency induced lifespan extension. The enhanced protection of protein homeostasis may be insufficient to slow aging, and there may be other mechanisms that contribute to the increased longevity in response to mitochondrial dysfunctions.
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Yaguang
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Sixi
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Ma
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Yao
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Dayan
authors.initials: D
authors.lastname: Sun
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China. Electronic address: jxlu313@163.com.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Lu
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics*; D004579:Electron Transport / Q000235:genetics*; D008017:Life Expectancy; D008136:Longevity / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D056811:Unfolded Protein Response / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D027682:Cation Transport Proteins; D024101:Mitochondrial Proteins; C000589467:Nuo-6 protein, C elegans; C572390:mfn-1 protein, C elegans; D011494:Protein Kinases; C578467:gcn-2 protein, C elegans
keywords: C. elegans; GCN-2; Lifespan; Mitochondrial dysfunctions; Mitochondrial unfolded protein response; Protein homeostasis