Gellerich 2012 Biochem J

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Gellerich FN, Gizatullina Z, Trumbeckaite S, Korzeniewski B, Gaynutdinov T, Seppet E, Vielhaber S, Heinze HJ, Striggow F (2012) Cytosolic Ca2+ regulates the energisation of isolated brain mitochondria by formation of pyruvate through the malate-aspartate shuttle. Biochem J 443:747-55.

» PMID: 22295911

Gellerich FN, Gizatullina Z, Trumbeckaite S, Korzeniewski B, Gaynutdinov T, Seppet E, Vielhaber S, Heinze HJ, Striggow F (2012) Biochem J

Abstract: The glutamate-dependent respiration of isolated brain mitochondria (BM) is regulated by cytosolic Ca2+ (Ca2+cyt) (S0.5 = 225 ± 22 nM) through its effects on aralar. We now also demonstrate that the a-glycerophosphate-dependent respiration is controlled by Ca2+cyt (S0.5 = 60 ± 10 nM). At higher Ca2+cyt (< 600 nM), BM accumulate Ca2+ which enhances the rate of action of intramitochondrial dehydrogenases. The highest Ca2+-induced increments of state 3 respiration decrease with substrate in the order glutamate < a-ketoglutarate < isocitrate < a-glycerophosphate < pyruvate. Whereas the oxidation of pyruvate is only slightly influenced by Ca2+cyt, we show that the formation of pyruvate is tightly controlled by Ca2+cyt. Through its common substrate couple NADH/NAD+, the formation of pyruvate by lactate dehydrogenase (LDH) is linked to the malate-aspartate shuttle (MAS) with aralar as a central component. A rise of Ca2+cyt in a reconstituted system consisting of BM, cytosolic enzymes of MAS and LDH causes an up to five-fold enhancement of OXPHOS rates that is due to an increased substrate supply, acting in a manner similar to a "gas pedal". In contrast, mitochondrial Ca2+ (Ca2+mit) regulates the oxidation rates of substrates which are present within mitochondrial matrix. We postulate that Ca2+cyt is a key factor in adjusting the mitochondrial energisation to the requirements of intact neurons.

Keywords: Llactate dehydrogenase (LDH), Malate-aspartate shuttle (MAS), Mitochondrial substrate supply, Aralar, Pyruvate precursors, Intramitochondrial dehydrogenases

O2k-Network Lab: DE Magdeburg Gellerich FN


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Organism: Mouse  Tissue;cell: Nervous system  Preparation: Isolated mitochondria  Enzyme: Complex III 

Coupling state: OXPHOS 

HRR: Oxygraph-2k