Gellerich 2012 Biochem J
| 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 [Epub ahead of print]. |
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 ± 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 ± 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
• O2k-Network Lab: DE Magdeburg Gellerich FN
Labels:
Stress:z in prep"z in prep" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Mouse Tissue;cell: Neurons; Brain"Neurons; Brain" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property. 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: z in prep"z in prep" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property., Complex III Regulation: z in prep"z in prep" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
HRR: Oxygraph-2k
