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Sci Signal. 2018 Apr 24;11(527). pii: eaap8526. doi: 10.1126/scisignal.aap8526.

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

Lu X1,2,3,4,5, Altshuler-Keylin S1,2,3,6, Wang Q1,2,3, Chen Y1,2,3, Henrique Sponton C1,2,3,7, Ikeda K1,2,3, Maretich P1,2,3, Yoneshiro T1,2,3, Kajimura S8,2,3.

Author information

1
Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
2
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, San Francisco, CA 94143, USA.
3
Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA 94143, USA.
4
Medical Diagnostic Research Center, Jilin Province People's Hospital, Changchun, Jilin 130021, China.
5
Department of Immunology, Jilin University, Changchun, Jilin 130021, China.
6
Department of Physiological Chemistry, Genentech Inc., South San Francisco, CA 94080, USA.
7
Obesity and Comorbidities Research Center, University of Campinas (UNICAMP), Campinas, Sao Paulo 13084-970, Brazil.
8
Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA. shingo.kajimura@ucsf.edu.

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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