TY  - JOUR
AU  - Gellerich, Frank Norbert
AU  - Gizatullina, Zemfira
AU  - Trumbekaite, Sonata
AU  - Korzeniewski, Bernard
AU  - Gaynutdinov, Timur
AU  - Seppet, Enn
AU  - Vielhaber, Stefan
AU  - Heinze, Hans-Jochen
AU  - Striggow, Frank
TI  - Cytosolic Ca2+ regulates the energization of isolated brain mitochondria by formation of pyruvate through the malate-aspartate shuttle.
JO  - Biochemical journal
VL  - 443
IS  - 3
SN  - 0264-6021
CY  - London
PB  - Portland Press67261
M1  - DZNE-2020-02836
SP  - 747-755
PY  - 2012
AB  - 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.
KW  - Animals
KW  - Aspartic Acid: metabolism
KW  - Brain: metabolism
KW  - Calcium: metabolism
KW  - Cytosol: metabolism
KW  - Kinetics
KW  - Malates: metabolism
KW  - Mice
KW  - Mitochondria: metabolism
KW  - Oxidative Phosphorylation
KW  - Pyruvic Acid: metabolism
KW  - Malates (NLM Chemicals)
KW  - Aspartic Acid (NLM Chemicals)
KW  - malic acid (NLM Chemicals)
KW  - Pyruvic Acid (NLM Chemicals)
KW  - Calcium (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:22295911
DO  - DOI:10.1042/BJ20110765
UR  - https://pub.dzne.de/record/136514
ER  -