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

Experimental Gerontology
Yaguang RenJianxin Lu

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 def...Continue Reading

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Citations

Jun 25, 2015·Biogerontology·Guillermo López-LluchPlácido Navas
Nov 23, 2017·Nature Reviews. Molecular Cell Biology·Tomer Shpilka, Cole M Haynes
Oct 13, 2016·The Biochemical Journal·Ignacio AmigoAlicia J Kowaltowski
Jul 29, 2017·Scientific Reports·Joseph R DanieleAndrew Dillin
Sep 10, 2019·Drug Discovery Today·Wilson Wen Bin GohGuillaume Thibault

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