title: Cytosolic Ca2+ regulates the energization of isolated brain mitochondria by formation of pyruvate through the malate-aspartate shuttle.
abstract: The glutamate-dependent respiration of isolated BM (brain mitochondria) is regulated by Ca2+(cyt) (cytosolic Ca2+) (S0.5=225±22 nM) through its effects on aralar. We now also demonstrate that the α-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 intramitochondrial dehydrogenases. The Ca2+-induced increments of state 3 respiration decrease with substrate in the order glutamate>α-oxoglutarate>isocitrate>α-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 LDH (lactate dehydrogenase) is linked to the MAS (malate-aspartate shuttle) with aralar as a central component. A rise in Ca2+(cyt) in a reconstituted system consisting of BM, cytosolic enzymes of MAS and LDH causes an up to 5-fold enhancement of OXPHOS (oxidative phosphorylation) rates that is due to an increased substrate supply, acting in a manner similar to a 'gas pedal'. In contrast, Ca2+(mit) (intramitochondrial Ca2+) regulates the oxidation rates of substrates which are present within the mitochondrial matrix. We postulate that Ca2+(cyt) is a key factor in adjusting the mitochondrial energization to the requirements of intact neurons.
authors.affiliation: Department of Behavioral Neurology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany. frank.gellerich@med.ovgu.de
authors.forename: Frank Norbert
authors.initials: FN
authors.lastname: Gellerich
authors.forename: Zemfira
authors.initials: Z
authors.lastname: Gizatullina
authors.forename: Sonata
authors.initials: S
authors.lastname: Trumbekaite
authors.forename: Bernard
authors.initials: B
authors.lastname: Korzeniewski
authors.forename: Timur
authors.initials: T
authors.lastname: Gaynutdinov
authors.forename: Enn
authors.initials: E
authors.lastname: Seppet
authors.forename: Stefan
authors.initials: S
authors.lastname: Vielhaber
authors.forename: Hans-Jochen
authors.initials: HJ
authors.lastname: Heinze
authors.forename: Frank
authors.initials: F
authors.lastname: Striggow
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D007700:Kinetics; D008293:Malates / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D019289:Pyruvic Acid / Q000378:metabolism*
chemical_list: D008293:Malates; D001224:Aspartic Acid; C030298:malic acid; D019289:Pyruvic Acid; D002118:Calcium