Journal article
Metabolic clearance of oxaloacetate and mitochondrial complex II respiration: Divergent control in skeletal muscle and brown adipose tissue
Biochimica et biophysica acta. Bioenergetics, Vol.1864(1), pp.148930-148930
01/01/2023
DOI: 10.1016/j.bbabio.2022.148930
PMCID: PMC10225247
PMID: 36272463
Abstract
At low inner mitochondrial membrane potential (AT) oxaloacetate (OAA) accumulates in the organelles concurrently with decreased complex II-energized respiration. This is consistent with AT -dependent OAA in-hibition 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 AT 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 AT increased complex II (succinate)-energized respiration in muscle but had little effect in IBAT mito-chondria. The transaminase inhibitor, aminooxyacetic acid, increased OAA concentrations and impaired succinate-energized respiration in muscle but not IBAT mitochondria at low but not high AT. 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 AT, 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.
Details
- Title: Subtitle
- Metabolic clearance of oxaloacetate and mitochondrial complex II respiration: Divergent control in skeletal muscle and brown adipose tissue
- Creators
- Adam J. Rauckhorst - University of IowaLiping Yu - University of IowaBrian D. Fink - University of IowaRitu Som - Univ Iowa, Iowa City Vet Affairs Med Ctr, Dept Internal Med Endocrinol & Metab, Iowa City, IA 52242 USAEric B. Taylor - University of IowaWilliam I. Sivitz - Univ Iowa, Iowa City Vet Affairs Med Ctr, Dept Internal Med Endocrinol & Metab, Iowa City, IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- Biochimica et biophysica acta. Bioenergetics, Vol.1864(1), pp.148930-148930
- DOI
- 10.1016/j.bbabio.2022.148930
- PMID
- 36272463
- PMCID
- PMC10225247
- NLM abbreviation
- Biochim Biophys Acta Bioenerg
- ISSN
- 0005-2728
- eISSN
- 1879-2650
- Publisher
- Elsevier
- Number of pages
- 13
- Grant note
- Iowa Fraternal Order of the Eagles (WIS) 2 I01 BX000285-06 / U.S. Department of Veterans Affairs, Biomedical Laboratory Research and Development Service; US Department of Veterans Affairs 1 R01 DK123043-01A1; R01 DK104998 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 01/01/2023
- Academic Unit
- Molecular Physiology and Biophysics; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Medicine Administration; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984383278502771
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