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Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis

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Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis

dc.contributor.author	Moreno Torres, Marta
dc.contributor.author	Ma, Tao
dc.contributor.author	Lynes, Matthew D.
dc.contributor.author	Larsen, Michael
dc.contributor.author	Karavaeva, Iuliia
dc.contributor.author	Havelund, Jesper F.
dc.contributor.author	Nielsen, Carsten H.
dc.contributor.author	Jedrychowski, Mark P
dc.contributor.author	Sustarsic, Elahu G.
dc.contributor.author	Lundh, Morten
dc.contributor.author	Plucinska, Kaja
dc.contributor.author	Jespersen, Naja Z.
dc.contributor.author
dc.date.accessioned	2023-05-22T06:39:45Z
dc.date.available	2023-05-22T06:39:45Z
dc.date.issued	2018
dc.identifier.citation	Moreno Torres, Marta Ma, Tao Lynes, Matthew D. Larsen, Michael Karavaeva, Iuliia Havelund, Jesper F. Nielsen, Carsten H. Jedrychowski, Mark P Sustarsic, Elahu G. Lundh, Morten Plucinska, Kaja Jespersen, Naja Z. 2018 Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis Cell Metabolism 28 3 159 174
dc.identifier.uri	https://hdl.handle.net/10550/86737
dc.description.abstract	Activation of energy expenditure in thermogenic fat is a promising strategy to improve metabolic health, yet the dynamic processes that evoke this response are poorly understood. Here we show that synthesis of the mitochondrial phospholipid cardiolipin is indispensable for stimulating and sustaining thermogenic fat function. Cardiolipin biosynthesis is robustly induced in brown and beige adipose upon cold exposure. Mimicking this response through overexpression of cardiolipin synthase (Crls1) enhances energy consumption in mouse and human adipocytes. Crls1 deficiency in thermogenic adipocytes diminishes inducible mitochondrial uncoupling and elicits a nuclear transcriptional response through endoplasmic reticulum stress-mediated retrograde communication. Cardiolipin depletion in brown and beige fat abolishes adipose thermogenesis and glucose uptake, which renders animals insulin resistant. We further identify a rare human CRLS1 variant associated with insulin resistance and show that adipose CRLS1 levels positively correlate with insulin sensitivity. Thus, adipose cardiolipin has a powerful impact on organismal energy homeostasis through thermogenic fat bioenergetics.
dc.language.iso	eng
dc.relation.ispartof	Cell Metabolism, 2018, vol. 28, num. 3, p. 159-174
dc.subject	Bioquímica
dc.subject	Biologia
dc.title	Cardiolipin synthesis in brown and beige fat mitochondria is essential for systemic energy homeostasis
dc.type	journal article
dc.date.updated	2023-05-22T06:39:45Z
dc.identifier.doi	10.1016/j.cmet.2018.05.003
dc.identifier.idgrec	158855
dc.rights.accessRights	open access