%0 Journal Article
%A Gellerich, Frank Norbert
%A Gizatullina, Zemfira
%A Trumbekaite, Sonata
%A Korzeniewski, Bernard
%A Gaynutdinov, Timur
%A Seppet, Enn
%A Vielhaber, Stefan
%A Heinze, Hans-Jochen
%A Striggow, Frank
%T Cytosolic Ca2+ regulates the energization of isolated brain mitochondria by formation of pyruvate through the malate-aspartate shuttle.
%J Biochemical journal
%V 443
%N 3
%@ 0264-6021
%C London
%I Portland Press67261
%M DZNE-2020-02836
%P 747-755
%D 2012
%X 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.
%K Animals
%K Aspartic Acid: metabolism
%K Brain: metabolism
%K Calcium: metabolism
%K Cytosol: metabolism
%K Kinetics
%K Malates: metabolism
%K Mice
%K Mitochondria: metabolism
%K Oxidative Phosphorylation
%K Pyruvic Acid: metabolism
%K Malates (NLM Chemicals)
%K Aspartic Acid (NLM Chemicals)
%K malic acid (NLM Chemicals)
%K Pyruvic Acid (NLM Chemicals)
%K Calcium (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:22295911
%R 10.1042/BJ20110765
%U https://pub.dzne.de/record/136514