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Komlodi 2017 Abstract MITOEAGLE Barcelona

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COST Action MITOEAGLE
Succinate dehydrogenase regulation via oxaloacetate in brain mitochondria.

Link: MITOEAGLE

Komlodi T, Horvath G, Svab G, Doerrier C, Sumbalova Z, Tretter L, Gnaiger E (2017)

Event: MITOEAGLE Barcelona 2017

COST Action MITOEAGLE

Succinate dehydrogenase (SDH) is the only enzyme participating both in the respiratory chain and the citrate-cycle. SDH has a well-known metabolic role but according to recent studies it also participates in hypoxia-induced cellular reactions and tumorigenesis [1]. Our preliminary experiments showed that at low concentrations of succinate, ADP inhibited O2 consumption in brain mitochondria, but this phenomenon was not detected in kidney and liver mitochondria. The aim of the present study was to investigate the organ specific regulation of SDH in order to clarify the regulatory mechanisms responsible for the ADP induced respiratory depression. Experiments were carried out on isolated guinea pig brain and kidney mitochondria. Mitochondrial respiration was measured by Clark-type electrode. SDH, malic enzyme, phosphoenolpyruvate-carboxykinase (PEPCK) and hydroxy-oxoglutarate aldolase (HOGA) [2] enzymes activities were determined spectrophotometrically. The maximal O2 consumption in the presence of succinate was similar in brain and kidney mitochondria at saturating conditions. At lower concentrations of succinate the cause of inhibition was the endogenously produced oxaloacetate (OA) [3]. However, OA inhibited SDH in both organs to a similar extent [4,5]. Addition of rotenone or pyruvate abolished the respiration inhibition, because rotenone decreased the OA production and pyruvate increased the elimination. The presence of malic enzyme and HOGA decreased the malate or OA and increased pyruvate concentration, respectively. PEPCK directly eliminated OA and produced phospoenolpyruvate. The reason behind the organ specificity of ADP-mediated inhibition of succinate respiration could be the various mechanism and efficacy of OA elimination in the two organs. Our results showed that PEPCK and HOGA enzymes take part in the regulation of OA concentration, which is the main metabolic inhibitor of SDH [5].


β€’ Bioblast editor: Kandolf G β€’ O2k-Network Lab: AT Innsbruck Gnaiger E, AT Innsbruck OROBOROS, HU Budapest Tretter L


Labels: MiParea: Respiration 


Organism: Guinea pig  Tissue;cell: Nervous system, Kidney  Preparation: Isolated mitochondria  Enzyme: Complex II;succinate dehydrogenase  Regulation: ADP  Coupling state: OXPHOS  Pathway:HRR: Oxygraph-2k 


Affiliations

Komlodi(1), Svab(1), Doerrier(2,3), Sumbalova(2,3), Tretter(1), Gnaiger(2,3)
  1. Dept Med Biochem, MTA-SE Lab Neurochem, Semmelweis Univ, Budapest, Hungary
  2. OROBOROS INTSRUMENTS, Innsbruck, Austria
  3. D. Swarovski Research Lab, Dept Visceral, Transplant Thoracic Surgery, Medical Univ Innsbruck, Austria. [email protected]


References

  1. Tretter LA, Patocs A, Chinopoulos C (2016) Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis. Biochim Biophys Acta 1857:1086-101.
  2. Gupta SC, Dekker EE (1984) Malyl-CoA formation in the NAD-, CoASH-, and alpha-ketoglutarate dehydrogenase-dependent oxidation of 2-keto-4-hydroxyglutarate. Possible coupled role of this reaction with 2-keto-4-hydroxyglutarate aldolase activity in a pyruvate-catalyzed cyclic oxidation of glyoxylate. J Biol Chem 259:10012-9.
  3. Chance B, Hagihara B (1962) Activation and inhibition of succinate oxidation following adenosine diphosphate supplements to pigeon heart mitochondria. J Biol Chem 237:3540-5.

4. Stepanova A, et al. (2016) Differential susceptibility of mitochondrial complex II to inhibition by oxaloacetate in brain and heart. Biochim Biophys Acta, 1857(9): 1561-8. 5. Wojtczak AB (1969) Inhibitory action of oxaloacetate on succinate oxidation in rat-liver mitochondria and the mechanism of its reversal. Biochim Biophys Acta, 172(1): 52-65.