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Publication : Parkin controls brown adipose tissue plasticity in response to adaptive thermogenesis.

First Author  Cairó M Year  2019
Journal  EMBO Rep Volume  20
Issue  5 PubMed ID  30867164
Mgi Jnum  J:274628 Mgi Id  MGI:6296949
Doi  10.15252/embr.201846832 Citation  Cairo M, et al. (2019) Parkin controls brown adipose tissue plasticity in response to adaptive thermogenesis. EMBO Rep 20(5)
abstractText  Parkin is an ubiquitin-E3 ligase that acts as a key component of the cellular machinery for mitophagy. We show here that Parkin expression is reciprocally regulated in brown adipose tissue in relation to thermogenic activity. Thermogenic stimuli repress Parkin gene expression via transcriptional mechanisms that are elicited by noradrenergic and PPARalpha-mediated pathways that involve intracellular lipolysis in brown adipocytes. Parkin-KO mice show over-activated brown adipose tissue thermogenic activity and exhibit improved metabolic parameters, especially when fed a high-fat diet. Deacclimation, which is the return of a cold-adapted mouse to a thermoneutral temperature, dramatically induces mitophagy in brown adipocytes, with a concomitant induction of Parkin levels. We further reveal that Parkin-KO mice exhibit defects in the degradative processing of mitochondrial proteins in brown adipose tissue in response to deacclimation. These results suggest that the transcriptional control of Parkin in brown adipose tissue may contribute to modulating the mitochondrial mass and activity for adaptation to thermogenic requirements.
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