Yu 2023 Biochim Biophys Acta Bioenerg

Yu L, Fink BD, Som R, Rauckhorst AJ, Taylor EB, Sivitz WI (2022) Metabolic clearance of oxaloacetate and mitochondrial complex II respiration: Divergent control in skeletal muscle and brown adipose tissue. https://doi.org/10.1016/j.bbabio.2022.148930

» Biochim Biophys Acta Bioenerg 1864:148930. PMID: 36272463 Open Access

Yu Liping, Fink Brian D, Som Ritu, Rauckhorst Adam J, Taylor Eric B, Sivitz William I (2022) Biochim Biophys Acta Bioenerg

Abstract: 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. • Keywords: Brown adipose tissue, Mitochondria, Mitochondrial complex II, Muscle, Oxaloacetate, Succinate dehydrogenase • Bioblast editor: Plangger M • O2k-Network Lab: US IA Iowa City Sivitz WI

Labels: MiParea: Respiration 

Organism: Mouse  Tissue;cell: Fat  Preparation: Isolated mitochondria 

Pathway: S  HRR: Oxygraph-2k 

2022-11