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Cell Rep DOI:10.1016/j.celrep.2019.04.013

Exploring the In Vivo Role of the Mitochondrial Calcium Uniporter in Brown Fat Bioenergetics.

Publication TypeJournal Article
Year of Publication2019
AuthorsFlicker, D, Sancak, Y, Mick, E, Goldberger, O, Mootha, VK
JournalCell Rep
Volume27
Issue5
Pages1364-1375.e5
Date Published2019 Apr 30
ISSN2211-1247
Abstract

The mitochondrial calcium uniporter has been proposed to coordinate the organelle's energetics with calcium signaling. Uniporter current has previously been reported to be extremely high in brown adipose tissue (BAT), yet it remains unknown how the uniporter contributes to BAT physiology. Here, we report the generation and characterization of a mouse model lacking Mcu, the pore forming subunit of the uniporter, specifically in BAT (BAT-Mcu-KO). BAT-Mcu-KO mice lack uniporter-based calcium uptake in BAT mitochondria but exhibit unaffected cold tolerance, diet-induced obesity, and transcriptional response to cold in BAT. Unexpectedly, we found in wild-type animals that cold powerfully activates the ATF4-dependent integrated stress response (ISR) in BAT and upregulates circulating FGF21 and GDF15, raising the hypothesis that the ISR partly underlies the pleiotropic effects of BAT on systemic metabolism. Our study demonstrates that the uniporter is largely dispensable for BAT thermogenesis and demonstrates activation of the ISR in BAT in response to cold.

DOI10.1016/j.celrep.2019.04.013
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31042465?dopt=Abstract

Alternate JournalCell Rep
PubMed ID31042465