Yu 2023 Biochim Biophys Acta Bioenerg: Difference between revisions
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|year=2022 | |year=2022 | ||
|journal=Biochim Biophys Acta Bioenerg | |journal=Biochim Biophys Acta Bioenerg | ||
|abstract=At low inner mitochondrial membrane potential (ฮฮจ) oxaloacetate (OAA) accumulates in the organelles concurrently with decreased complex II-energized respiration. This is consistent with ฮฮจ-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 | |abstract=At low inner mitochondrial membrane potential (ฮฮจ) oxaloacetate (OAA) accumulates in the organelles concurrently with decreased complex II-energized respiration. This is consistent with ฮฮจ-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 O<sub>2</sub> flux and, further, that this would occur in both ฮฮจ 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 ฮฮจ 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 ฮฮจ. 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 ฮฮจ, 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 | |keywords=Brown adipose tissue, Mitochondria, Mitochondrial complex II, Muscle, Oxaloacetate, Succinate dehydrogenase | ||
|editor=[[Plangger M]] | |editor=[[Plangger M]] | ||
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{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration | ||
|organism=Mouse | |||
|tissues=Fat | |||
|preparations=Isolated mitochondria | |||
|couplingstates=LEAK | |||
|pathways=N, NS | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=2022-11 | |additional=2022-11 | ||
}} | }} |
Revision as of 15:51, 7 November 2022
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 |
ยป 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 (ฮฮจ) oxaloacetate (OAA) accumulates in the organelles concurrently with decreased complex II-energized respiration. This is consistent with ฮฮจ-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 ฮฮจ 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 ฮฮจ 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 ฮฮจ. 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 ฮฮจ, 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. โข Keywords: Brown adipose tissue, Mitochondria, Mitochondrial complex II, Muscle, Oxaloacetate, Succinate dehydrogenase โข Bioblast editor: Plangger M โข O2k-Network Lab: US IA Iowa City Sivitz WI
Labels: MiParea: Respiration
Organism: Mouse
Tissue;cell: Fat
Preparation: Isolated mitochondria
Coupling state: LEAK
Pathway: N, NS
HRR: Oxygraph-2k
2022-11