The E3 ligase MARCH5 is a PPARγ target gene that regulates mitochondria and metabolism in adipocytes
| Autor: | Aldons J. Lusis, Simon T. Bond, Darren C. Henstridge, Bronwyn A. Kingwell, Sarah C. Moody, Yingying Liu, Andrea L. Hevener, Brian G. Drew, Anna C. Calkin, Paul Gregorevic, Mete Civelek, Claudio J. Villanueva |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Physiology Ubiquitin-Protein Ligases Endocrinology Diabetes and Metabolism Peroxisome proliferator-activated receptor Mitochondrion Mitochondrial Proteins Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine 3T3-L1 Cells Physiology (medical) Internal medicine Adipocyte Mitophagy Adipocytes medicine Animals Humans Obesity MARCH5 Metabolic Syndrome Mice Knockout chemistry.chemical_classification Adipogenesis biology Membrane Proteins Lipid metabolism Middle Aged Mitochondria Ubiquitin ligase Cell biology PPAR gamma 030104 developmental biology Endocrinology Adipose Tissue chemistry Gene Knockdown Techniques biology.protein 030217 neurology & neurosurgery Research Article |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 316:E293-E304 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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