The activation of protein homeostasis protective mechanisms perhaps is not responsible for lifespan extension caused by deficiencies of mitochondrial proteins in C. elegans

• Published in: Experimental gerontology Vol. 65; pp. 53 - 57
• Main Authors: Ren, Yaguang, Chen, Sixi, Ma, Mengmeng, Yao, Xiuping, Sun, Dayan, Li, Bin, Lu, Jianxin
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.05.2015
• Subjects: Aging - physiology; Animals; C. elegans; Caenorhabditis elegans; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cation Transport Proteins - genetics; Electron Transport - genetics; GCN-2; Life Expectancy; Lifespan; Longevity - genetics; Mitochondrial dysfunctions; Mitochondrial Proteins - metabolism; Mitochondrial unfolded protein response; Protein homeostasis; Protein Kinases - metabolism; Unfolded Protein Response - physiology; C. elegans; Protein homeostasis; Lifespan; Mitochondrial dysfunctions; Mitochondrial unfolded protein response; GCN-2
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2015.03.005

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 (UPRmt) and GCN-2 kinase mediated nutrient-sensing pathway. However, we investigated four genes which encode well-defined mitochondrial proteins and found that: (i) UPRmt 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 UPRmt pathway did not repress mfn-1, cco-1, or nuo-6 RNAi induced lifespan extension; (iii) The activation of UPRmt 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 UPRmt 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. •UPRmt could not explain mitochondrial deficiency induced lifespan extension.•The lifespan extension caused by mitochondrial dysfunctions is not relied on GCN-2.•Enhanced protection of protein homeostasis may be insufficient to slow aging.