Difference between revisions of "Gellerich 2009 PLoS One"
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|year=2009 | |year=2009 | ||
|journal=PLoS One | |journal=PLoS One | ||
|abstract=We present unexpected and novel results revealing that glutamate-dependent oxidative phosphorylation (OXPHOS) of brain mitochondria is exclusively and efficiently activated by extramitochondrial Ca<sup>2+</sup> in physiological concentration ranges (S<sub>0.5</sub>= 360 nM Ca<sup>2+</sup>). This regulation was not affected by RR, an inhibitor of the mitochondrial Ca<sup>2+</sup> uniporter. Active respiration is regulated by glutamate supply to mitochondria via aralar, a mitochondrial glutamate/aspartate carrier with regulatory Ca<sup>2+</sup>-binding sites in the mitochondrial intermembrane space providing full access to cytosolic Ca<sup>2+</sup>. At micromolar concentrations, Ca<sup>2+</sup> can also enter the intramitochondrial matrix and activate specific dehydrogenases. However, the latter mechanism is less efficient than extramitochondrial Ca<sup>2+</sup> regulation of respiration/OXPHOS via aralar. These results imply a new mode of glutamate-dependent OXPHOS regulation as a demand-driven regulation of mitochondrial function. This regulation involves the mitochondrial glutamate/aspartate carrier aralar which controls mitochondrial substrate supply according to the level of extramitochondrial Ca<sup>2+</sup>. | |abstract=We present unexpected and novel results revealing that glutamate-dependent oxidative phosphorylation (OXPHOS) of brain mitochondria is exclusively and efficiently activated by extramitochondrial Ca<sup>2+</sup> in physiological concentration ranges (S<sub>0.5</sub>= 360 nM Ca<sup>2+</sup>). This regulation was not affected by RR, an inhibitor of the mitochondrial Ca<sup>2+</sup> uniporter. Active respiration is regulated by glutamate supply to mitochondria via aralar, a mitochondrial glutamate/aspartate carrier with regulatory Ca<sup>2+</sup>-binding sites in the mitochondrial intermembrane space providing full access to cytosolic Ca<sup>2+</sup>. At micromolar concentrations, Ca<sup>2+</sup> can also enter the intramitochondrial matrix and activate specific dehydrogenases. However, the latter mechanism is less efficient than extramitochondrial Ca<sup>2+</sup> regulation of respiration/OXPHOS via aralar. These results imply a new mode of glutamate-dependent OXPHOS regulation as a demand-driven regulation of mitochondrial function. This regulation involves the mitochondrial glutamate/aspartate carrier aralar which controls mitochondrial substrate supply according to the level of extramitochondrial Ca<sup>2+</sup>. | ||
|keywords=Glutamate/aspartate carrier aralar, Extramitochondrial Ca (2+), Brain mitochondria | |keywords=Glutamate/aspartate carrier aralar, Extramitochondrial Ca (2+), Brain mitochondria | ||
|mipnetlab=EE_Tartu_Seppet E, DE_Magdeburg_Gellerich FN, | |||
|discipline=Mitochondrial Physiology, Biomedicine | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
| | |instruments=Oxygraph-2k | ||
|injuries=RONS; Oxidative Stress | |injuries=RONS; Oxidative Stress | ||
|tissues=Neurons; Brain | |tissues=Neurons; Brain | ||
| Line 16: | Line 17: | ||
|kinetics=Inhibitor; Uncoupler | |kinetics=Inhibitor; Uncoupler | ||
|topics=Respiration; OXPHOS; ETS Capacity | |topics=Respiration; OXPHOS; ETS Capacity | ||
| | |discipline=Mitochondrial Physiology, Biomedicine | ||
}} | }} | ||
Revision as of 09:26, 12 August 2011
| Gellerich FN, Gizatullina Z, Arandarcikaite O, Jerzembek D, Vielhaber S, Seppet E, Striggow F (2009) Extramitochondrial Ca2+ in the nanomolar range regulates glutamate-dependent oxidative phosphorylation on demand. PloS One. 4(12): e8181. |
Gellerich FN, Gizatullina Z, Arandarcikaite O, Jerzembek D, Vielhaber S, Seppet E, Striggow F (2009) PLoS One
Abstract: We present unexpected and novel results revealing that glutamate-dependent oxidative phosphorylation (OXPHOS) of brain mitochondria is exclusively and efficiently activated by extramitochondrial Ca2+ in physiological concentration ranges (S0.5= 360 nM Ca2+). This regulation was not affected by RR, an inhibitor of the mitochondrial Ca2+ uniporter. Active respiration is regulated by glutamate supply to mitochondria via aralar, a mitochondrial glutamate/aspartate carrier with regulatory Ca2+-binding sites in the mitochondrial intermembrane space providing full access to cytosolic Ca2+. At micromolar concentrations, Ca2+ can also enter the intramitochondrial matrix and activate specific dehydrogenases. However, the latter mechanism is less efficient than extramitochondrial Ca2+ regulation of respiration/OXPHOS via aralar. These results imply a new mode of glutamate-dependent OXPHOS regulation as a demand-driven regulation of mitochondrial function. This regulation involves the mitochondrial glutamate/aspartate carrier aralar which controls mitochondrial substrate supply according to the level of extramitochondrial Ca2+. • Keywords: Glutamate/aspartate carrier aralar, Extramitochondrial Ca (2+), Brain mitochondria
• O2k-Network Lab: EE_Tartu_Seppet E, DE_Magdeburg_Gellerich FN
Labels:
Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" 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.
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.
Enzyme: Inner mtMembrane Transporter"Inner mtMembrane Transporter" 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. Regulation: 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
