Gellerich 2012 Biochem J: Difference between revisions
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|abstract=The glutamate-dependent respiration of isolated brain mitochondria (BM) is regulated by cytosolic Ca2+ (Ca2+cyt) (S0.5 = 225 ยฑ 22 nM) through its effects on aralar. We now also demonstrate that the a-glycerophosphate-dependent respiration is controlled by Ca2+cyt (S0.5 = 60 ยฑ 10 nM). At higher Ca2+cyt (< 600 nM), BM accumulate Ca2+ which enhances the rate of action of intramitochondrial dehydrogenases. The highest Ca2+-induced increments of state 3 respiration decrease with substrate in the order glutamate < a-ketoglutarate < isocitrate < a-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 lactate dehydrogenase (LDH) is linked to the malate-aspartate shuttle (MAS) with aralar as a central component. A rise of Ca2+cyt in a reconstituted system consisting of BM, cytosolic enzymes of MAS and LDH causes an up to five-fold enhancement of OXPHOS rates that is due to an increased substrate supply, acting in a manner similar to a "gas pedal". In contrast, mitochondrial Ca2+ (Ca2+mit) regulates the oxidation rates of substrates which are present within mitochondrial matrix. We postulate that Ca2+cyt is a key factor in adjusting the mitochondrial energisation to the requirements of intact neurons. | |abstract=The glutamate-dependent respiration of isolated brain mitochondria (BM) is regulated by cytosolic Ca2+ (Ca2+cyt) (S0.5 = 225 ยฑ 22 nM) through its effects on aralar. We now also demonstrate that the a-glycerophosphate-dependent respiration is controlled by Ca2+cyt (S0.5 = 60 ยฑ 10 nM). At higher Ca2+cyt (< 600 nM), BM accumulate Ca2+ which enhances the rate of action of intramitochondrial dehydrogenases. The highest Ca2+-induced increments of state 3 respiration decrease with substrate in the order glutamate < a-ketoglutarate < isocitrate < a-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 lactate dehydrogenase (LDH) is linked to the malate-aspartate shuttle (MAS) with aralar as a central component. A rise of Ca2+cyt in a reconstituted system consisting of BM, cytosolic enzymes of MAS and LDH causes an up to five-fold enhancement of OXPHOS rates that is due to an increased substrate supply, acting in a manner similar to a "gas pedal". In contrast, mitochondrial Ca2+ (Ca2+mit) regulates the oxidation rates of substrates which are present within mitochondrial matrix. We postulate that Ca2+cyt is a key factor in adjusting the mitochondrial energisation to the requirements of intact neurons. | ||
|keywords=lactate dehydrogenase (LDH); malate-aspartate shuttle (MAS); mitochondrial substrate supply; aralar; pyruvate precursors; intramitochondrial dehydrogenases | |keywords=lactate dehydrogenase (LDH); malate-aspartate shuttle (MAS); mitochondrial substrate supply; aralar; pyruvate precursors; intramitochondrial dehydrogenases | ||
|mipnetlab=DE_Magdeburg_Gellerich FN | |mipnetlab=DE_Magdeburg_Gellerich FN | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|organism=Mouse | |organism=Mouse | ||
|tissues=Nervous system | |tissues=Nervous system | ||
|preparations=Isolated Mitochondria | |preparations=Isolated Mitochondria | ||
|enzymes=Complex III | |||
|couplingstates=OXPHOS | |couplingstates=OXPHOS | ||
| | |instruments=Oxygraph-2k | ||
}} | }} |
Revision as of 15:23, 28 August 2014
Gellerich FN, Gizatullina Z, Trumbeckaite S, Korzeniewski B, Gaynutdinov T, Seppet E, Vielhaber S, Heinze HJ, Striggow F (2012) Cytosolic Ca2+ regulates the energisation of isolated brain mitochondria by formation of pyruvate through the malate-aspartate shuttle. Biochem J 443: 747-755. |
Gellerich FN, Gizatullina Z, Trumbeckaite S, Korzeniewski B, Gaynutdinov T, Seppet E, Vielhaber S, Heinze HJ, Striggow F (2012) Biochem J
Abstract: The glutamate-dependent respiration of isolated brain mitochondria (BM) is regulated by cytosolic Ca2+ (Ca2+cyt) (S0.5 = 225 ยฑ 22 nM) through its effects on aralar. We now also demonstrate that the a-glycerophosphate-dependent respiration is controlled by Ca2+cyt (S0.5 = 60 ยฑ 10 nM). At higher Ca2+cyt (< 600 nM), BM accumulate Ca2+ which enhances the rate of action of intramitochondrial dehydrogenases. The highest Ca2+-induced increments of state 3 respiration decrease with substrate in the order glutamate < a-ketoglutarate < isocitrate < a-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 lactate dehydrogenase (LDH) is linked to the malate-aspartate shuttle (MAS) with aralar as a central component. A rise of Ca2+cyt in a reconstituted system consisting of BM, cytosolic enzymes of MAS and LDH causes an up to five-fold enhancement of OXPHOS rates that is due to an increased substrate supply, acting in a manner similar to a "gas pedal". In contrast, mitochondrial Ca2+ (Ca2+mit) regulates the oxidation rates of substrates which are present within mitochondrial matrix. We postulate that Ca2+cyt is a key factor in adjusting the mitochondrial energisation to the requirements of intact neurons. โข Keywords: lactate dehydrogenase (LDH); malate-aspartate shuttle (MAS); mitochondrial substrate supply; aralar; pyruvate precursors; intramitochondrial dehydrogenases
โข O2k-Network Lab: DE_Magdeburg_Gellerich FN
Labels:
Organism: Mouse
Tissue;cell: Nervous system
Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property.
Enzyme: Complex III
Coupling state: OXPHOS
HRR: Oxygraph-2k