Mitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression

Abstract Mitochondrial respiration plays a crucial role in determining the metabolic state of brown adipose tissue (BAT), due to its direct roles in thermogenesis, as well as through additional mechanisms. Here, we show that respiration-dependent retrograde signaling from mitochondria to nucleus con...

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Autores principales:	Minwoo Nam, Thomas E. Akie, Masato Sanosaka, Siobhan M. Craige, Shashi Kant, John F. Keaney Jr, Marcus P. Cooper
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a66f49441c9b45cab90f279e62a62661
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spelling	oai:doaj.org-article:a66f49441c9b45cab90f279e62a626612021-12-02T12:30:37ZMitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression10.1038/s41598-017-01879-x2045-2322https://doaj.org/article/a66f49441c9b45cab90f279e62a626612017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01879-xhttps://doaj.org/toc/2045-2322Abstract Mitochondrial respiration plays a crucial role in determining the metabolic state of brown adipose tissue (BAT), due to its direct roles in thermogenesis, as well as through additional mechanisms. Here, we show that respiration-dependent retrograde signaling from mitochondria to nucleus contributes to genetic and metabolic reprogramming of BAT. In mouse BAT, ablation of LRPPRC (LRP130), a potent regulator of mitochondrial transcription and respiratory capacity, triggers down-regulation of thermogenic genes, promoting a storage phenotype in BAT. This retrograde regulation functions by inhibiting the recruitment of PPARγ to the regulatory elements of thermogenic genes. Reducing cytosolic Ca2+ reverses the attenuation of thermogenic genes in brown adipocytes with impaired respiratory capacity, while induction of cytosolic Ca2+ is sufficient to attenuate thermogenic gene expression, indicating that cytosolic Ca2+ mediates mitochondria-nucleus crosstalk. Our findings suggest respiratory capacity governs thermogenic gene expression and BAT function via mitochondria-nucleus communication, which in turn leads to either a thermogenic or storage mode.Minwoo NamThomas E. AkieMasato SanosakaSiobhan M. CraigeShashi KantJohn F. Keaney JrMarcus P. CooperNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Minwoo Nam Thomas E. Akie Masato Sanosaka Siobhan M. Craige Shashi Kant John F. Keaney Jr Marcus P. Cooper Mitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression
description	Abstract Mitochondrial respiration plays a crucial role in determining the metabolic state of brown adipose tissue (BAT), due to its direct roles in thermogenesis, as well as through additional mechanisms. Here, we show that respiration-dependent retrograde signaling from mitochondria to nucleus contributes to genetic and metabolic reprogramming of BAT. In mouse BAT, ablation of LRPPRC (LRP130), a potent regulator of mitochondrial transcription and respiratory capacity, triggers down-regulation of thermogenic genes, promoting a storage phenotype in BAT. This retrograde regulation functions by inhibiting the recruitment of PPARγ to the regulatory elements of thermogenic genes. Reducing cytosolic Ca2+ reverses the attenuation of thermogenic genes in brown adipocytes with impaired respiratory capacity, while induction of cytosolic Ca2+ is sufficient to attenuate thermogenic gene expression, indicating that cytosolic Ca2+ mediates mitochondria-nucleus crosstalk. Our findings suggest respiratory capacity governs thermogenic gene expression and BAT function via mitochondria-nucleus communication, which in turn leads to either a thermogenic or storage mode.
format	article
author	Minwoo Nam Thomas E. Akie Masato Sanosaka Siobhan M. Craige Shashi Kant John F. Keaney Jr Marcus P. Cooper
author_facet	Minwoo Nam Thomas E. Akie Masato Sanosaka Siobhan M. Craige Shashi Kant John F. Keaney Jr Marcus P. Cooper
author_sort	Minwoo Nam
title	Mitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression
title_short	Mitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression
title_full	Mitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression
title_fullStr	Mitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression
title_full_unstemmed	Mitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression
title_sort	mitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a66f49441c9b45cab90f279e62a62661
work_keys_str_mv	AT minwoonam mitochondrialretrogradesignalingconnectsrespiratorycapacitytothermogenicgeneexpression AT thomaseakie mitochondrialretrogradesignalingconnectsrespiratorycapacitytothermogenicgeneexpression AT masatosanosaka mitochondrialretrogradesignalingconnectsrespiratorycapacitytothermogenicgeneexpression AT siobhanmcraige mitochondrialretrogradesignalingconnectsrespiratorycapacitytothermogenicgeneexpression AT shashikant mitochondrialretrogradesignalingconnectsrespiratorycapacitytothermogenicgeneexpression AT johnfkeaneyjr mitochondrialretrogradesignalingconnectsrespiratorycapacitytothermogenicgeneexpression AT marcuspcooper mitochondrialretrogradesignalingconnectsrespiratorycapacitytothermogenicgeneexpression
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Mitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression

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