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Metabolic clearance of oxaloacetate and mitochondrial complex II respiration: Divergent control in skeletal muscle and brown adipose tissue.
Yu, Liping; Fink, Brian D; Som, Ritu; Rauckhorst, Adam J; Taylor, Eric B; Sivitz, William I.
Afiliación
  • Yu L; Department of Biochemistry and Molecular Biology, University of Iowa, Iowa City, IA 52242, USA; Carver College of Medicine NMR Core Facility, University of Iowa, Iowa City, IA 52242, USA.
  • Fink BD; Department of Internal Medicine/Endocrinology and Metabolism, University of Iowa and the Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, USA.
  • Som R; Department of Internal Medicine/Endocrinology and Metabolism, University of Iowa and the Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, USA.
  • Rauckhorst AJ; Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
  • Taylor EB; Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
  • Sivitz WI; Department of Internal Medicine/Endocrinology and Metabolism, University of Iowa and the Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242, USA. Electronic address: william-sivitz@uiowa.edu.
Biochim Biophys Acta Bioenerg ; 1864(1): 148930, 2023 01 01.
Article en En | MEDLINE | ID: mdl-36272463
At low inner mitochondrial membrane potential (ΔΨ) oxaloacetate (OAA) accumulates in the organelles concurrently with decreased complex II-energized respiration. This is consistent with ΔΨ-dependent OAA inhibition of succinate dehydrogenase. To assess the metabolic importance of this process, we tested the hypothesis that perturbing metabolic clearance of OAA in complex II-energized mitochondria would alter O2 flux and, further, that this would occur in both ΔΨ and tissue-dependent fashion. We carried out respiratory and metabolite studies in skeletal muscle and interscapular brown adipose tissue (IBAT) directed at the effect of OAA transamination to aspartate (catalyzed by the mitochondrial form of glutamic-oxaloacetic transaminase, Got2) on complex II-energized respiration. Addition of low amounts of glutamate to succinate-energized mitochondria at low ΔΨ increased complex II (succinate)-energized respiration in muscle but had little effect in IBAT mitochondria. The transaminase inhibitor, aminooxyacetic acid, increased OAA concentrations and impaired succinate-energized respiration in muscle but not IBAT mitochondria at low but not high ΔΨ. Immunoblotting revealed that Got2 expression was far greater in muscle than IBAT mitochondria. Because we incidentally observed metabolism of OAA to pyruvate in IBAT mitochondria, more so than in muscle mitochondria, we also examined the expression of mitochondrial oxaloacetate decarboxylase (ODX). ODX was detected only in IBAT mitochondria. In summary, at low but not high ΔΨ, mitochondrial transamination clears OAA preventing loss of complex II respiration: a process far more active in muscle than IBAT mitochondria. We also provide evidence that OAA decarboxylation clears OAA to pyruvate in IBAT mitochondria.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Succinato Deshidrogenasa / Ácido Oxaloacético Idioma: En Revista: Biochim Biophys Acta Bioenerg Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Succinato Deshidrogenasa / Ácido Oxaloacético Idioma: En Revista: Biochim Biophys Acta Bioenerg Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos