Article (Scientific journals)
Two Conserved Histone Demethylases Regulate Mitochondrial Stress-Induced Longevity.
Merkwirth, Carsten; Jovaisaite, Virginija; Durieux, Jenni et al.
2016In Cell, 165 (5), p. 1209-1223
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Keywords :
Animals; Caenorhabditis elegans/genetics/physiology; Caenorhabditis elegans Proteins/metabolism; Histone Demethylases/metabolism; Jumonji Domain-Containing Histone Demethylases/metabolism; Longevity; Mice; Mitochondria/metabolism; Transcription Factors/metabolism; Transcription, Genetic; Unfolded Protein Response
Abstract :
[en] Across eukaryotic species, mild mitochondrial stress can have beneficial effects on the lifespan of organisms. Mitochondrial dysfunction activates an unfolded protein response (UPR(mt)), a stress signaling mechanism designed to ensure mitochondrial homeostasis. Perturbation of mitochondria during larval development in C. elegans not only delays aging but also maintains UPR(mt) signaling, suggesting an epigenetic mechanism that modulates both longevity and mitochondrial proteostasis throughout life. We identify the conserved histone lysine demethylases jmjd-1.2/PHF8 and jmjd-3.1/JMJD3 as positive regulators of lifespan in response to mitochondrial dysfunction across species. Reduction of function of the demethylases potently suppresses longevity and UPR(mt) induction, while gain of function is sufficient to extend lifespan in a UPR(mt)-dependent manner. A systems genetics approach in the BXD mouse reference population further indicates conserved roles of the mammalian orthologs in longevity and UPR(mt) signaling. These findings illustrate an evolutionary conserved epigenetic mechanism that determines the rate of aging downstream of mitochondrial perturbations.
Disciplines :
Genetics & genetic processes
Author, co-author :
Merkwirth, Carsten
Jovaisaite, Virginija
Durieux, Jenni
Matilainen, Olli
Jordan, Sabine D.
Quiros, Pedro M.
Steffen, Kristan K.
Williams, Evan  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Mouchiroud, Laurent
Tronnes, Sarah U.
Murillo, Virginia
Wolff, Suzanne C.
Shaw, Reuben J.
Auwerx, Johan
Dillin, Andrew
More authors (5 more) Less
External co-authors :
yes
Language :
English
Title :
Two Conserved Histone Demethylases Regulate Mitochondrial Stress-Induced Longevity.
Publication date :
2016
Journal title :
Cell
ISSN :
1097-4172
Publisher :
Cell Press, United States - Massachusetts
Volume :
165
Issue :
5
Pages :
1209-1223
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2016 Elsevier Inc. All rights reserved.
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