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

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, Thomas Q.de Aguiar Vallim, Markku Laakso, Aldons J. Lusis, Andrea L. Hevener, Zhenqi Zhou

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish
Article number6661
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - 1 Dec 2022
Externally publishedYes

ASJC Scopus subject areas

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology

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