Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling

Abstract Mitochondrial dysfunction is usually associated with various metabolic disorders and ageing. However, salutary effects in response to mild mitochondrial perturbations have been reported in multiple organisms, whereas molecular regulators of cell-autonomous stress responses remain elusive. W...

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Autores principales:	Verena Coleman, Piangkwan Sa-Nguanmoo, Jeannette Koenig, Tim J. Schulz, Tilman Grune, Susanne Klaus, Anna P. Kipp, Mario Ost
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ddd25ebf61ac4caa96259ace3a1b59f0
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spelling	oai:doaj.org-article:ddd25ebf61ac4caa96259ace3a1b59f02021-12-02T15:08:41ZPartial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling10.1038/s41598-018-20901-42045-2322https://doaj.org/article/ddd25ebf61ac4caa96259ace3a1b59f02018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20901-4https://doaj.org/toc/2045-2322Abstract Mitochondrial dysfunction is usually associated with various metabolic disorders and ageing. However, salutary effects in response to mild mitochondrial perturbations have been reported in multiple organisms, whereas molecular regulators of cell-autonomous stress responses remain elusive. We addressed this question by asking whether the nuclear factor erythroid-derived-like 2 (Nrf2), a transcription factor and master regulator of cellular redox status is involved in adaptive physiological responses including muscle mitohormesis. Using a transgenic mouse model with skeletal muscle-specific mitochondrial uncoupling and oxidative phosphorylation (OXPHOS) inefficiency (UCP1-transgenic, TG) we show that additional genetic ablation of Nrf2 abolishes an adaptive muscle NAD(P)H quinone dehydrogenase 1 (NQO1) and catalase induction. Deficiency of Nrf2 also leads to decreased mitochondrial respiratory performance although muscle functional integrity, fiber-type profile and mitochondrial biogenesis were not significantly altered. Importantly, Nrf2 ablation did not abolish the induction of key genes and proteins of muscle integrated stress response including the serine, one-carbon cycle, and glycine synthesis (SOG) pathway in TG mice while further increasing glutathione peroxidase (GPX) activity linked to increased GPX1 protein levels. Conclusively, our results tune down the functions controlled by Nrf2 in muscle mitohormesis and oxidative stress defense during mitochondrial OXPHOS inefficiency.Verena ColemanPiangkwan Sa-NguanmooJeannette KoenigTim J. SchulzTilman GruneSusanne KlausAnna P. KippMario OstNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Verena Coleman Piangkwan Sa-Nguanmoo Jeannette Koenig Tim J. Schulz Tilman Grune Susanne Klaus Anna P. Kipp Mario Ost Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling
description	Abstract Mitochondrial dysfunction is usually associated with various metabolic disorders and ageing. However, salutary effects in response to mild mitochondrial perturbations have been reported in multiple organisms, whereas molecular regulators of cell-autonomous stress responses remain elusive. We addressed this question by asking whether the nuclear factor erythroid-derived-like 2 (Nrf2), a transcription factor and master regulator of cellular redox status is involved in adaptive physiological responses including muscle mitohormesis. Using a transgenic mouse model with skeletal muscle-specific mitochondrial uncoupling and oxidative phosphorylation (OXPHOS) inefficiency (UCP1-transgenic, TG) we show that additional genetic ablation of Nrf2 abolishes an adaptive muscle NAD(P)H quinone dehydrogenase 1 (NQO1) and catalase induction. Deficiency of Nrf2 also leads to decreased mitochondrial respiratory performance although muscle functional integrity, fiber-type profile and mitochondrial biogenesis were not significantly altered. Importantly, Nrf2 ablation did not abolish the induction of key genes and proteins of muscle integrated stress response including the serine, one-carbon cycle, and glycine synthesis (SOG) pathway in TG mice while further increasing glutathione peroxidase (GPX) activity linked to increased GPX1 protein levels. Conclusively, our results tune down the functions controlled by Nrf2 in muscle mitohormesis and oxidative stress defense during mitochondrial OXPHOS inefficiency.
format	article
author	Verena Coleman Piangkwan Sa-Nguanmoo Jeannette Koenig Tim J. Schulz Tilman Grune Susanne Klaus Anna P. Kipp Mario Ost
author_facet	Verena Coleman Piangkwan Sa-Nguanmoo Jeannette Koenig Tim J. Schulz Tilman Grune Susanne Klaus Anna P. Kipp Mario Ost
author_sort	Verena Coleman
title	Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling
title_short	Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling
title_full	Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling
title_fullStr	Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling
title_full_unstemmed	Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling
title_sort	partial involvement of nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/ddd25ebf61ac4caa96259ace3a1b59f0
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_version_	1718388094229544960

Partial involvement of Nrf2 in skeletal muscle mitohormesis as an adaptive response to mitochondrial uncoupling

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