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Parkin regulates adiposity by coordinating mitophagy with mitochondrial biogenesis in white adipocytes

Author

Listed:
  • Timothy M. Moore

    (University of California)

  • Lijing Cheng

    (University of California)

  • Dane M. Wolf

    (University of California
    University of Cambridge
    University of Cambridge, Cambridge Biomedical Campus)

  • Jennifer Ngo

    (University of California)

  • Mayuko Segawa

    (University of California
    University of Cambridge)

  • Xiaopeng Zhu

    (Department of Pediatrics UCLA Children’s Discovery and Innovation Institute, University of California
    Zhongshan Hospital, Fudan University)

  • Alexander R. Strumwasser

    (University of California)

  • Yang Cao

    (University of California)

  • Bethan L. Clifford

    (University of California)

  • Alice Ma

    (University of California)

  • Philip Scumpia

    (University of California)

  • Orian S. Shirihai

    (University of California)

  • Thomas Q. de Aguiar Vallim

    (University of California
    David Geffen School of Medicine, University of California
    University of California)

  • Markku Laakso

    (University of Eastern Finland)

  • Aldons J. Lusis

    (University of California
    University of California)

  • Andrea L. Hevener

    (University of California
    Veterans Administration Greater Los Angeles Healthcare System, Geriatric Research Education and Clinical Center (GRECC))

  • Zhenqi Zhou

    (University of California
    University of California)

Abstract

Parkin, an E3 ubiquitin ligase, plays an essential role in mitochondrial quality control. However, the mechanisms by which Parkin connects mitochondrial homeostasis with cellular metabolism in adipose tissue remain unclear. Here, we demonstrate that Park2 gene (encodes Parkin) deletion specifically from adipose tissue protects mice against high-fat diet and aging-induced obesity. Despite a mild reduction in mitophagy, mitochondrial DNA content and mitochondrial function are increased in Park2 deficient white adipocytes. Moreover, Park2 gene deletion elevates mitochondrial biogenesis by increasing Pgc1α protein stability through mitochondrial superoxide-activated NAD(P)H quinone dehydrogenase 1 (Nqo1). Both in vitro and in vivo studies show that Nqo1 overexpression elevates Pgc1α protein level and mitochondrial DNA content and enhances mitochondrial activity in mouse and human adipocytes. Taken together, our findings indicate that Parkin regulates mitochondrial homeostasis by balancing mitophagy and Pgc1α-mediated mitochondrial biogenesis in white adipocytes, suggesting a potential therapeutic target in adipocytes to combat obesity and obesity-associated disorders.

Suggested Citation

  • Timothy M. Moore & Lijing Cheng & Dane M. Wolf & Jennifer Ngo & Mayuko Segawa & Xiaopeng Zhu & Alexander R. Strumwasser & Yang Cao & Bethan L. Clifford & Alice Ma & Philip Scumpia & Orian S. Shirihai , 2022. "Parkin regulates adiposity by coordinating mitophagy with mitochondrial biogenesis in white adipocytes," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34468-2
    DOI: 10.1038/s41467-022-34468-2
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