Research ArticleMetabolism

Mitophagy controls beige adipocyte maintenance through a Parkin-dependent and UCP1-independent mechanism

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Sci. Signal.  24 Apr 2018:
Vol. 11, Issue 527, eaap8526
DOI: 10.1126/scisignal.aap8526

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A whitener for beige fat

White fat can undergo “browning” and acquire some of the energy-burning properties of brown fat in response to various stimuli, such as β3-adrenergic receptor activation. Mitophagy, a specialized autophagic process that degrades mitochondria, causes these beige adipocytes to reacquire the fat-storing characteristics of white adipocytes. Using mouse models and cultured beige adipocytes, Lu et al. (see also the Focus by Sarraf and Youle) found that Parkin, a factor that promotes the autophagy of damaged mitochondria, was also responsible for mitophagy in beige adipocytes, which triggered their reversion to white adipocytes. β3-Adrenergic receptor activation triggered the PKA-mediated phosphorylation of Parkin and prevented the recruitment of Parkin to mitochondria. These results not only identify a mechanism that could be targeted to maintain beige fat but also demonstrate that Parkin induces the mitophagy of undamaged mitochondria and thus has a role in adipose tissue under physiological conditions.

Abstract

Beige adipocytes are an inducible form of mitochondria-enriched thermogenic adipocytes that emerge in response to external stimuli, such as chronic cold exposure. We have previously shown that after the withdrawal of external stimuli, beige adipocytes directly acquire a white fat–like phenotype through autophagy-mediated mitochondrial degradation. We investigated the upstream pathway that mediates mitochondrial clearance and report that Parkin-mediated mitophagy plays a key role in the beige-to-white adipocyte transition. Mice genetically deficient in Park2 showed reduced mitochondrial degradation and retained thermogenic beige adipocytes even after the withdrawal of external stimuli. Norepinephrine signaling through the PKA pathway inhibited the recruitment of Parkin protein to mitochondria in beige adipocytes. However, mitochondrial proton uncoupling by uncoupling protein 1 (UCP1) was dispensable for Parkin recruitment and beige adipocyte maintenance. These results suggest a physiological mechanism by which external cues control mitochondrial homeostasis in thermogenic fat cells through mitophagy.

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