RT Journal Article
SR Electronic
T1 GPS2 regulates mitochondria biogenesis via mitochondrial retrograde signaling and chromatin remodeling of nuclear-encoded mitochondrial genes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 162297
DO 10.1101/162297
A1 Maria Dafne Cardamone
A1 Bogdan Tanasa
A1 Carly Cederquist
A1 Jiawen Huang
A1 Kiana Mahdaviani
A1 Wembo Li
A1 Michael G. Rosenfeld
A1 Marc Liesa
A1 Valentina Perissi
YR 2017
UL http://biorxiv.org/content/early/2017/07/11/162297.abstract
AB As most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-to-nucleus communication pathways are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a key transcriptional activator of nuclear-encoded mitochondrial genes in mammals. GPS2 regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of the nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and in brown adipose tissue from mice. In the nucleus, GPS2 recruitment to target gene promoters regulates histone H3K9 demethylation and RNA Polymerase II (POL2) activation through inhibition of Ubc13-mediated ubiquitination. Together, these findings reveal an unexpected layer of regulation of mitochondrial gene transcription as they uncover a novel mitochondria-nuclear communication pathway.