Abstract

Mild inhibition of mitochondrial respiration leads to longevity. Disruption of mitochondrial respiratory components extends lifespan in Caenorhabditis elegans, but the effects appear to be complex and the underlying mechanism for lifespan regulation by mitochondrial respiratory genes is still not fully understood. Here, we investigated the role of Y82E9BR.3, a worm homolog of the ATP synthase subunit C, in modulating longevity in C. elegans. We found that the Y82E9BR.3 protein is localized in mitochondria and expressed in various tissues throughout development. RNAi knockdown of Y82E9BR.3 extends lifespan, decreases the accumulation of lipofuscin, and affects various physiological processes, including development delay, reproduction impairment and slow behavior. Further tissue-specific RNAi analysis showed that the intestine is a crucial organ for the longevity effects conferred by Y82E9BR.3 RNAi. Moreover, we demonstrated that lifespan extension by Y82E9BR.3 RNAi is associated with reduced mitochondrial function, as well as the suppression of complex I activity in mitochondria. Unexpectedly, Y82E9BR.3 RNAi knock down did not influence the whole-worm ATP level. Our findings first reveal the crucial role of Y82E9BR.3 in mitochondrial function and the underlying mechanism of how Y82E9BR.3 regulates lifespan in C. elegans.

Details

Title
Genetic inhibition of an ATP synthase subunit extends lifespan in C. elegans
Author
Chen, Xu 1 ; Hwang, Wooseon 2 ; Dae-Eun Jeong 2 ; Ryu, Youngjae 3 ; Chang Man Ha 3 ; Lee, Seung-Jae V 4   VIAFID ORCID Logo  ; Liu, Lulu 1 ; He, Zhi Ming 1 

1  State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China 
2  Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea 
3  Brain Research Core Facilities, Korea Brain Research Institute, Daegu, South Korea 
4  Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea; Department of IT Convergence and Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea; School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea 
Pages
1-14
Publication year
2018
Publication date
Oct 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-018-32025-w
ProQuest document ID
2116411684
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.