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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Cheng, Lijing 
Wolf, Dane M 
Ngo, Jennifer 
Segawa, Mayuko 

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.

Description

Keywords

Mice, Humans, Animals, Mitophagy, Organelle Biogenesis, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adipocytes, White, Adiposity, Ubiquitin-Protein Ligases, Obesity, DNA, Mitochondrial

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Springer Science and Business Media LLC