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The E3 ligase MARCH5 is a PPARγ target gene that regulates mitochondria and metabolism in adipocytes

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Bond, ST, Moody, SC, Liu, Y, Civelek, M, Villanueva, CJ, Gregorevic, P, Kingwell, BA, Hevener, AL, Lusis, AJ, Henstridge, DC ORCID: 0000-0003-4988-767X, Calkin, AC and Drew, BG 2019 , 'The E3 ligase MARCH5 is a PPARγ target gene that regulates mitochondria and metabolism in adipocytes' , American Journal of Physiology: Endocrinology and Metabolism, vol. 316, no. 2 , E293-E304 , doi: 10.1152/ajpendo.00394.2018.

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Abstract

Mitochondrial dynamics refers to the constant remodeling of mitochondrial populations by multiple cellular pathways that help maintain mitochondrial health and function. Disruptions in mitochondrial dynamics often lead to mitochondrial dysfunction, which is frequently associated with disease in rodents and humans. Consistent with this, obesity is associated with reduced mitochondrial function in white adipose tissue, partly via alterations in mitochondrial dynamics. Several proteins, including the E3 ubiquitin ligase membrane-associated RING-CH-type finger 5 (MARCH5), are known to regulate mitochondrial dynamics; however, the role of these proteins in adipocytes has been poorly studied. Here, we show that MARCH5 is regulated by peroxisome proliferator-activated receptor-γ (PPARγ) during adipogenesis and is correlated with fat mass across a panel of genetically diverse mouse strains, in ob/ob mice, and in humans. Furthermore, manipulation of MARCH5 expression in vitro and in vivo alters mitochondrial function, affects cellular metabolism, and leads to differential regulation of several metabolic genes. Thus our data demonstrate an association between mitochondrial dynamics and metabolism that defines MARCH5 as a critical link between these interconnected pathways.

Item Type: Article
Authors/Creators:Bond, ST and Moody, SC and Liu, Y and Civelek, M and Villanueva, CJ and Gregorevic, P and Kingwell, BA and Hevener, AL and Lusis, AJ and Henstridge, DC and Calkin, AC and Drew, BG
Keywords: lipid metabolism, MARCH5, mitochondria, peroxisome proliferator activated receptor gamma, ligase, peroxisome proliferator activated receptor, ubiquitin protein ligase E3, adipocyte, adipogenesis, adipose tissue, animal cell
Journal or Publication Title: American Journal of Physiology: Endocrinology and Metabolism
Publisher: Amer Physiological Soc
ISSN: 0193-1849
DOI / ID Number: 10.1152/ajpendo.00394.2018
Copyright Information:

Copyright 2019 the American Physiological Society

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