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 M, Akie TE, Sanosaka M, Craige SM, Kant S, Keaney JF, Cooper MP. (2017). Mitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression. UMass Metabolic Network Publications. https://doi.org/10.1038/s41598-017-01879-x. Retrieved from https://escholarship.umassmed.edu/metnet_pubs/112
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.