Use este identificador para citar ou linkar para este item: https://locus.ufv.br//handle/123456789/22102
Tipo: Artigo
Título: On the role of the mitochondrial 2-oxoglutarate dehydrogenase complex in amino acid metabolism
Autor(es): Araújo, Wagner L.
Steinhauser, Dirk
Krall, Leonard
Fernie, Alisdair R.
Trofimova, Lidia
Mkrtchyan, Garik
Graf, Anastasia
Bunik, Victoria I.
Abstract: Mitochondria are tightly linked to cellular nutrient sensing, and provide not only energy, but also intermediates for the de novo synthesis of cellular compounds including amino acids. Mitochondrial metabolic enzymes as generators and/or targets of signals are therefore important players in the distribution of intermediates between catabolic and anabolic pathways. The highly regulated 2-oxoglutarate dehydrogenase complex (OGDHC) participates in glucose oxidation via the tricarboxylic acid cycle. It occupies an amphibolic branch point in the cycle, where the energy-producing reaction of the 2-oxoglutarate degradation competes with glutamate (Glu) synthesis via nitrogen incorporation into 2-oxoglutarate. To characterize the specific impact of the OGDHC inhibition on amino acid metabolism in both plant and animal mitochondria, a synthetic analog of 2-oxoglutarate, namely succinyl phosphonate (SP), was applied to living systems from different kingdoms, both in situ and in vivo. Using a high-throughput mass spectrometry-based approach, we showed that organisms possessing OGDHC respond to SP by significantly changing their amino acid pools. By contrast, cyanobacteria which lack OGDHC do not show perturbations in amino acids following SP treatment. Increases in Glu, 4-aminobutyrate and alanine represent the most universal change accompanying the 2-oxoglutarate accumulation upon OGDHC inhibition. Other amino acids were affected in a species-specific manner, suggesting specific metabolic rearrangements and substrate availability mediating secondary changes. Strong perturbation in the relative abundance of amino acids due to the OGDHC inhibition was accompanied by decreased protein content. Our results provide specific evidence of a considerable role of OGDHC in amino acid metabolism.
Palavras-chave: Amino acid metabolism
Mitochondria
2-oxoglutarate dehydrogenase
Succinyl phosphonate
TCA cycle
Editor: Amino Acids
Tipo de Acesso: Springer Vienna
URI: https://doi.org/10.1007/s00726-012-1392-x
http://www.locus.ufv.br/handle/123456789/22102
Data do documento: Fev-2013
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