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@ARTICLE{Gellerich:136514,
author = {Gellerich, Frank Norbert and Gizatullina, Zemfira and
Trumbekaite, Sonata and Korzeniewski, Bernard and
Gaynutdinov, Timur and Seppet, Enn and Vielhaber, Stefan and
Heinze, Hans-Jochen and Striggow, Frank},
title = {{C}ytosolic {C}a2+ regulates the energization of isolated
brain mitochondria by formation of pyruvate through the
malate-aspartate shuttle.},
journal = {Biochemical journal},
volume = {443},
number = {3},
issn = {0264-6021},
address = {London},
publisher = {Portland Press67261},
reportid = {DZNE-2020-02836},
pages = {747-755},
year = {2012},
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.},
keywords = {Animals / Aspartic Acid: metabolism / Brain: metabolism /
Calcium: metabolism / Cytosol: metabolism / Kinetics /
Malates: metabolism / Mice / Mitochondria: metabolism /
Oxidative Phosphorylation / Pyruvic Acid: metabolism /
Malates (NLM Chemicals) / Aspartic Acid (NLM Chemicals) /
malic acid (NLM Chemicals) / Pyruvic Acid (NLM Chemicals) /
Calcium (NLM Chemicals)},
cin = {AG Düzel / U Clinical Researchers - Magdeburg / AG
Striggow},
ddc = {540},
cid = {I:(DE-2719)5000006 / I:(DE-2719)7000000 /
I:(DE-2719)5000045},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342) / 344
- Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-344},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:22295911},
doi = {10.1042/BJ20110765},
url = {https://pub.dzne.de/record/136514},
}