Your browser doesn't support javascript.
loading
Drp1 controls complex II assembly and skeletal muscle metabolism by Sdhaf2 action on mitochondria.
Zhou, Zhenqi; Ma, Alice; Moore, Timothy M; Wolf, Dane M; Yang, Nicole; Tran, Peter; Segawa, Mayuko; Strumwasser, Alexander R; Ren, Wenjuan; Fu, Kai; Wanagat, Jonathan; van der Bliek, Alexander M; Crosbie-Watson, Rachelle; Liesa, Marc; Stiles, Linsey; Acin-Perez, Rebecca; Mahata, Sushil; Shirihai, Orian; Goodarzi, Mark O; Handzlik, Michal; Metallo, Christian M; Walker, David W; Hevener, Andrea L.
Afiliação
  • Zhou Z; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Ma A; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Moore TM; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wolf DM; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Yang N; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Tran P; Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Segawa M; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • Strumwasser AR; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Ren W; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Fu K; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Wanagat J; MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
  • van der Bliek AM; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Crosbie-Watson R; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Liesa M; Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Stiles L; Division of Geriatrics, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Acin-Perez R; Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
  • Mahata S; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Shirihai O; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Goodarzi MO; Center for Duchenne Muscular Dystrophy, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Handzlik M; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Metallo CM; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Walker DW; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Hevener AL; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Sci Adv ; 10(14): eadl0389, 2024 Apr 05.
Article em En | MEDLINE | ID: mdl-38569044
ABSTRACT
The dynamin-related guanosine triphosphatase, Drp1 (encoded by Dnm1l), plays a central role in mitochondrial fission and is requisite for numerous cellular processes; however, its role in muscle metabolism remains unclear. Here, we show that, among human tissues, the highest number of gene correlations with DNM1L is in skeletal muscle. Knockdown of Drp1 (Drp1-KD) promoted mitochondrial hyperfusion in the muscle of male mice. Reduced fatty acid oxidation and impaired insulin action along with increased muscle succinate was observed in Drp1-KD muscle. Muscle Drp1-KD reduced complex II assembly and activity as a consequence of diminished mitochondrial translocation of succinate dehydrogenase assembly factor 2 (Sdhaf2). Restoration of Sdhaf2 normalized complex II activity, lipid oxidation, and insulin action in Drp1-KD myocytes. Drp1 is critical in maintaining mitochondrial complex II assembly, lipid oxidation, and insulin sensitivity, suggesting a mechanistic link between mitochondrial morphology and skeletal muscle metabolism, which is clinically relevant in combatting metabolic-related diseases.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Succinato Desidrogenase / Insulinas Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Succinato Desidrogenase / Insulinas Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article