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Difference between revisions of "Gellerich 2010 Biochim Biophys Acta"

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(Created page with "{{Publication |title=Gellerich FN, Gizatullina Z, Trumbeckaite S, Nguyen HP, Pallas T, Arandarcikaite O, Vielhaber S, Seppet E, Striggow F (2010) The regulation of OXPHOS by extr...")
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|journal=Biochim. Biophys. Acta
|journal=Biochim. Biophys. Acta
|abstract=Despite extensive research, the regulation of mitochondrial function is still not understood completely. Ample evidence shows that cytosolic Ca2+ has a strategic task in co-ordinating the cellular work load and the regeneration of ATP by mitochondria. Currently, the paradigmatic view is that Cacyt2+ taken up by the Ca2+ uniporter activates the matrix enzymes pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and isocitrate dehydrogenase. However, we have recently found that Ca2+ regulates the glutamate-dependent state 3 respiration by the supply of glutamate to mitochondria via aralar, a mitochondrial glutamate/aspartate carrier. Since this activation is not affected by ruthenium red, glutamate transport into mitochondria is controlled exclusively by extramitochondrial Ca2+. Therefore, this discovery shows that besides intramitochondrial also extramitochondrial Ca2+ regulates oxidative phosphorylation. This new mechanism acts as a mitochondrial "gas pedal", supplying the OXPHOS with substrate on demand. These results are in line with recent findings of Satrustegui and Palmieri showing that aralar as part of the malate-aspartate shuttle is involved in the Ca2+-dependent transport of reducing hydrogen equivalents (from NADH) into mitochondria. This review summarises results and evidence as well as hypothetical interpretations of data supporting the view that at the surface of mitochondria different regulatory Ca2+-binding sites exist and can contribute to cellular energy homeostasis. Moreover, on the basis of our own data, we propose that these surface Ca2+-binding sites may act as targets for neurotoxic proteins such as mutated huntingtin and others. The binding of these proteins to Ca2+-binding sites can impair the regulation by Ca2+, causing energetic depression and neurodegeneration.
|abstract=Despite extensive research, the regulation of mitochondrial function is still not understood completely. Ample evidence shows that cytosolic Ca2+ has a strategic task in co-ordinating the cellular work load and the regeneration of ATP by mitochondria. Currently, the paradigmatic view is that Cacyt2+ taken up by the Ca2+ uniporter activates the matrix enzymes pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and isocitrate dehydrogenase. However, we have recently found that Ca2+ regulates the glutamate-dependent state 3 respiration by the supply of glutamate to mitochondria via aralar, a mitochondrial glutamate/aspartate carrier. Since this activation is not affected by ruthenium red, glutamate transport into mitochondria is controlled exclusively by extramitochondrial Ca2+. Therefore, this discovery shows that besides intramitochondrial also extramitochondrial Ca2+ regulates oxidative phosphorylation. This new mechanism acts as a mitochondrial "gas pedal", supplying the OXPHOS with substrate on demand. These results are in line with recent findings of Satrustegui and Palmieri showing that aralar as part of the malate-aspartate shuttle is involved in the Ca2+-dependent transport of reducing hydrogen equivalents (from NADH) into mitochondria. This review summarises results and evidence as well as hypothetical interpretations of data supporting the view that at the surface of mitochondria different regulatory Ca2+-binding sites exist and can contribute to cellular energy homeostasis. Moreover, on the basis of our own data, we propose that these surface Ca2+-binding sites may act as targets for neurotoxic proteins such as mutated huntingtin and others. The binding of these proteins to Ca2+-binding sites can impair the regulation by Ca2+, causing energetic depression and neurodegeneration.
|keywords=oxidative phosphorylation, egulation Intramitochondrial calcium Extramitochondrial calcium Glutamate respiration Aralar Pyruvate dehydrogenase Ξ±-Ketoglutarate dehydrogenase Isocitrate dehydrogenase ATP-Mg/Pi carrier FAD-glycerol-3-phosphate dehydrogenase Ca2+ uniporter F0F1ATPase Porin Permeability transition pore Transgenic Huntington rat, R6/2 mice
|keywords=oxidative phosphorylation, regulation, intramitochondrial calcium, extramitochondrial calcium, glutamate respiration, aralar, pyruvate dehydrogenase, Ξ±-Ketoglutarate dehydrogenase, isocitrate dehydrogenase, ATP-Mg/Pi carrier, FAD-glycerol-3-phosphate dehydrogenase, Ca2+ uniporter, F0F1ATPase, porin, permeability transition pore, transgenic Huntington rat, R6/2 mice
|mipnetlab=DE_Magdeburg_Gellerich FN
|mipnetlab=DE_Magdeburg_Gellerich FN
}}
}}
{{Labeling}}
{{Labeling
|instruments=Oxygraph-2k
|organism=Rat
|tissues=Neurons; Brain
|preparations=Isolated Mitochondria
}}

Revision as of 11:02, 1 September 2011

Publications in the MiPMap
Gellerich FN, Gizatullina Z, Trumbeckaite S, Nguyen HP, Pallas T, Arandarcikaite O, Vielhaber S, Seppet E, Striggow F (2010) The regulation of OXPHOS by extramitochondrial calcium. Biochim Biophys Acta.1797(6-7):1018-1027.

Β» PMID20144582:

Gellerich FN, Gizatullina Z, Trumbeckaite S, Nguyen HP, Pallas T, Arandarcikaite O, Vielhaber S, Seppet E, Striggow F (2010) Biochim. Biophys. Acta

Abstract: Despite extensive research, the regulation of mitochondrial function is still not understood completely. Ample evidence shows that cytosolic Ca2+ has a strategic task in co-ordinating the cellular work load and the regeneration of ATP by mitochondria. Currently, the paradigmatic view is that Cacyt2+ taken up by the Ca2+ uniporter activates the matrix enzymes pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase and isocitrate dehydrogenase. However, we have recently found that Ca2+ regulates the glutamate-dependent state 3 respiration by the supply of glutamate to mitochondria via aralar, a mitochondrial glutamate/aspartate carrier. Since this activation is not affected by ruthenium red, glutamate transport into mitochondria is controlled exclusively by extramitochondrial Ca2+. Therefore, this discovery shows that besides intramitochondrial also extramitochondrial Ca2+ regulates oxidative phosphorylation. This new mechanism acts as a mitochondrial "gas pedal", supplying the OXPHOS with substrate on demand. These results are in line with recent findings of Satrustegui and Palmieri showing that aralar as part of the malate-aspartate shuttle is involved in the Ca2+-dependent transport of reducing hydrogen equivalents (from NADH) into mitochondria. This review summarises results and evidence as well as hypothetical interpretations of data supporting the view that at the surface of mitochondria different regulatory Ca2+-binding sites exist and can contribute to cellular energy homeostasis. Moreover, on the basis of our own data, we propose that these surface Ca2+-binding sites may act as targets for neurotoxic proteins such as mutated huntingtin and others. The binding of these proteins to Ca2+-binding sites can impair the regulation by Ca2+, causing energetic depression and neurodegeneration. β€’ Keywords: oxidative phosphorylation, regulation, intramitochondrial calcium, extramitochondrial calcium, glutamate respiration, aralar, pyruvate dehydrogenase, Ξ±-Ketoglutarate dehydrogenase, isocitrate dehydrogenase, ATP-Mg/Pi carrier, FAD-glycerol-3-phosphate dehydrogenase, Ca2+ uniporter, F0F1ATPase, porin, permeability transition pore, transgenic Huntington rat, R6/2 mice

β€’ O2k-Network Lab: DE_Magdeburg_Gellerich FN


Labels:


Organism: Rat  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. 



HRR: Oxygraph-2k