Parkin regulates adiposity by coordinating mitophagy with mitochondrial biogenesis in white adipocytes
| Autor: | 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 |
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| Přispěvatelé: | Moore, Timothy M [0000-0003-4250-3370], Scumpia, Philip [0000-0002-2563-2042], Shirihai, Orian S [0000-0001-8466-3431], Lusis, Aldons J [0000-0001-9013-0228], Zhou, Zhenqi [0000-0001-6560-9704], Apollo - University of Cambridge Repository |
| Rok vydání: | 2022 |
| Předmět: |
Ubiquitin-Protein Ligases
1.1 Normal biological development and functioning Adipocytes White 38/90 General Physics and Astronomy White Neurodegenerative DNA Mitochondrial General Biochemistry Genetics and Molecular Biology 38/91 82/80 Mice 14/34 42/89 Underpinning research Adipocytes Genetics Animals Humans 631/443/319 Obesity 14/19 631/337/458/582 692/699/2743/393 Metabolic and endocrine Adiposity Nutrition Organelle Biogenesis Parkinson's Disease Multidisciplinary article Mitophagy Neurosciences DNA General Chemistry Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha 692/4017 Mitochondrial Brain Disorders 13/51 140/131 64/60 |
| Zdroj: | Nature communications, vol 13, iss 1 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-022-34468-2 |
| Popis: | Funder: UCLA Intercampus Medical Genetics Training Program (T32GM008243), NRSA predoctoral fellowship (F31DK108657), Carl V. Gisolfi Memorial Research grant from the American College of Sports Medicine, and a predoctoral graduate student award from the Dornsife College at the University of Southern California. Funder: EMBO long-term fellowship ALTF 828-2021 Funder: DK120342, DK117850 Funder: DK109724, P30DK063491 Funder: NIDDK DK125354 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. |
| Databáze: | OpenAIRE |
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