Division of Cardiovascular Medicine, Department of Medicine; UMass Metabolic Network
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Molecular Biology
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 PPARgamma 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.
Energy metabolism, Gene expression
DOI of Published Version
Sci Rep. 2017 May 17;7(1):2013. doi: 10.1038/s41598-017-01879-x. Link to article on publisher's site
Nam, Minwoo; Akie, Thomas E.; Sanosaka, Masato; Craige, Siobhan M.; Kant, Shashi; Keaney, John F. Jr.; and Cooper, Marcus P., "Mitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression" (2017). UMass Metabolic Network Publications. 112.
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