Mitochondrial retrograde signaling connects respiratory capacity to thermogenic gene expression

作者：Nam Minwoo; Akie Thomas E; Sanosaka Masato; Craige Siobhan M; Kant Shashi; Keaney John F Jr^*; Cooper Marcus P^*

来源：Scientific Reports, 2017, 7(1): 2013.

DOI：10.1038/s41598-017-01879-x

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 PPAR. 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 mitochondrianucleus communication, which in turn leads to either a thermogenic or storage mode.

• 出版日期2017-5-17