Two Conserved Histone Demethylases Regulate Mitochondrial Stress-Induced Longevity
| Autor: | Carsten Merkwirth, Jenni Durieux, Kristan K. Steffen, Sarah U. Tronnes, Johan Auwerx, Olli Matilainen, Evan G. Williams, Laurent Mouchiroud, Sabine D. Jordan, Suzanne Wolff, Virginia Murillo, Reuben J. Shaw, Andrew Dillin, Pedro M. Quirós, Virginija Jovaisaite |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Jumonji Domain-Containing Histone Demethylases Aging Transcription Genetic 1.1 Normal biological development and functioning media_common.quotation_subject Longevity Mitochondrion Biology Medical and Health Sciences Article General Biochemistry Genetics and Molecular Biology Epigenesis Genetic Mice 03 medical and health sciences Genetic Underpinning research Transcription (biology) Mitochondrial unfolded protein response Mitochondria/metabolism Genetics Humans Animals Transcription Factors/metabolism Caenorhabditis elegans/genetics/physiology Caenorhabditis elegans Caenorhabditis elegans Proteins media_common Histone Demethylases PHF8 Biological Sciences Mitochondria 030104 developmental biology Proteostasis Unfolded Protein Response Unfolded protein response Jumonji Domain-Containing Histone Demethylases/metabolism Caenorhabditis elegans Proteins/metabolism Genetics & genetic processes [F10] [Life sciences] Generic health relevance Histone Demethylases/metabolism Génétique & processus génétiques [F10] [Sciences du vivant] Transcription Transcription Factors Developmental Biology |
| Zdroj: | Cell, vol 165, iss 5 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2016.04.012 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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