Journal Article

DZNE-2020-02836

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cytosolic Ca2+ regulates the energization of isolated brain mitochondria by formation of pyruvate through the malate-aspartate shuttle.

Gellerich, F. N. (Corresponding author) ; Gizatullina, Z. ; Trumbekaite, S. ; Korzeniewski, B. ; Gaynutdinov, T. ; Seppet, E. ; Vielhaber, S.DZNE* ; Heinze, H.-J.DZNE* ; Striggow, F. (Last author)DZNE*

2012
Portland Press67261 London

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Please use a persistent id in citations: doi:10.1042/BJ20110765

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.

Keyword(s): Animals (MeSH) ; Aspartic Acid: metabolism (MeSH) ; Brain: metabolism (MeSH) ; Calcium: metabolism (MeSH) ; Cytosol: metabolism (MeSH) ; Kinetics (MeSH) ; Malates: metabolism (MeSH) ; Mice (MeSH) ; Mitochondria: metabolism (MeSH) ; Oxidative Phosphorylation (MeSH) ; Pyruvic Acid: metabolism (MeSH) ; Malates ; Aspartic Acid ; malic acid ; Pyruvic Acid ; Calcium

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Contributing Institute(s):

1. Clinical Neurophysiology and Memory (AG Düzel)
2. U Clinical Researchers - Magdeburg (U Clinical Researchers - Magdeburg)
3. Neurodegeneration and Intervention Strategies (AG Striggow)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
2. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2012

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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