Difference between revisions of "Gellerich 2013 Abstract MiP2013"
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|year=2013 | |year=2013 | ||
|event=MiP2013 | |event=MiP2013 | ||
|abstract= | |abstract=Cytosolic calcium (Ca2+cyt) has a strategic task in co-ordinating cellular work load and ATP regeneration (OXPHOS) but the mechanisms were not completely understood. Up to now the paradigmatic view was that Ca2+ after its uptake by the Ca2+ uniporter activates PDH, ICDH and -KGDH within the matrix. However we have shown by computer simulation that these effects are insufficient to explain the in vivo results [1]. Moreover, we have recently shown that Ca2+cyt in low nM concentration range (S0.05 = 225 ± 22 nM) exclusively regulates the glutamate-dependent state 3 respiration (state 3glu/mal) of isolated brain mitochondria (BM) via aralar [2-7], the mitochondrial glutamate/aspartate carrier. Whereas the state 3pyr/mal is only slightly influenced by Ca2+cyt we detected that pyruvate formation by the malate aspartate shuttle (MAS) is tightly controlled by Ca2+cyt [6,7]. Through its common substrate couple NADH/NAD+, the formation of pyruvate by LDH or glycolysis is linked to MAS with Aralar as a central component. A rise of Ca2+cyt in a reconstituted MAS causes an up to five-fold enhancement of OXPHOS rates due to an increased substrate supply, acting as a metabolic pyruvate supply unit which we called “gas pedal”, in contrast, intramitochondrial Ca2+ modulates the oxidation rates only of those substrate molecules which are already present within the mitochondrial matrix. | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
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|preparations=Isolated Mitochondria | |preparations=Isolated Mitochondria | ||
|enzymes=Inner mtMembrane Transporter | |enzymes=Inner mtMembrane Transporter | ||
|topics=Calcium, Ion;substrate transport | |topics=Calcium, Flux control, Ion;substrate transport | ||
|couplingstates=OXPHOS | |couplingstates=OXPHOS | ||
|substratestates=CI | |substratestates=CI |
Revision as of 10:48, 17 August 2013
Gellerich FN, Korzeniewski B, Gizatullina Z, Debska-Vielhaber G, Gainutdinov T, König R, Reymann K, Vielhaber S(2013) The mitochondrial gas pedal, a unique property of neurons exists also in heart and skeletal muscle but not in astrocytes. New evidences by in silico investigations and (patho-)physiological consequences. Mitochondr Physiol Network 18.08. |
Link:
Gellerich FN, Korzeniewski B, Gizatullina Z, Debska-Vielhaber G, Gainutdinov T, König R, Reymann K, Vielhaber S (2013)
Event: MiP2013
Cytosolic calcium (Ca2+cyt) has a strategic task in co-ordinating cellular work load and ATP regeneration (OXPHOS) but the mechanisms were not completely understood. Up to now the paradigmatic view was that Ca2+ after its uptake by the Ca2+ uniporter activates PDH, ICDH and -KGDH within the matrix. However we have shown by computer simulation that these effects are insufficient to explain the in vivo results [1]. Moreover, we have recently shown that Ca2+cyt in low nM concentration range (S0.05 = 225 ± 22 nM) exclusively regulates the glutamate-dependent state 3 respiration (state 3glu/mal) of isolated brain mitochondria (BM) via aralar [2-7], the mitochondrial glutamate/aspartate carrier. Whereas the state 3pyr/mal is only slightly influenced by Ca2+cyt we detected that pyruvate formation by the malate aspartate shuttle (MAS) is tightly controlled by Ca2+cyt [6,7]. Through its common substrate couple NADH/NAD+, the formation of pyruvate by LDH or glycolysis is linked to MAS with Aralar as a central component. A rise of Ca2+cyt in a reconstituted MAS causes an up to five-fold enhancement of OXPHOS rates due to an increased substrate supply, acting as a metabolic pyruvate supply unit which we called “gas pedal”, in contrast, intramitochondrial Ca2+ modulates the oxidation rates only of those substrate molecules which are already present within the mitochondrial matrix.
Labels: MiParea: Respiration
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: 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: Calcium, Flux control, Ion;substrate transport Coupling state: OXPHOS
HRR: Oxygraph-2k
MiP2013
Affiliations and author contributions
1 - Dept of Neurology, Otto von Guericke University of Magdeburg, Germany;
2 - Jagiellonian University, Krakow, Poland;
3 - German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany.
Email: [email protected]
References
- Korzeniewski B (2007) Regulation of oxidative phosphorylation through parallel activation. Biophys Chem 129: 93-110.
- Gellerich FN, Gizatullina Z, Nguyen HP, Trumbeckaite S, Vielhaber S, Seppet E, Zierz S, Landwehrmeyer B, Riess O, von Hörsten S, Striggow F (2008) Impaired regulation of brain mitochondria by extramitochondrial Ca2+ in transgenic Huntington disease rats. J Biol Chem 283: 30715-30724.
- 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: e8181..
- 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: 1018-1027.
- 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, Gainutdinov T, Muth K, Seppet E, Orynbayeva Z,Vielhaber S (2013) The control of brain mitochondrial energization by cytosolic calcium: the mitochondrial gas pedal. IUBMB-Life 65: 180-190.
- Satrústegui J, Pardo B, Del Arco A. (2007) Mitochondrial transporters as novel targets for intracellular calcium signaling. Physiol Rev 87: 29-67.
- Ikeda M, Sugiyama T, Wallace CS, Gompf HS, Yoshioka T, Miyawaki A, Allen CN. (2003) Circadian dynamics of cytosolic and nuclear Ca2+ in single suprachiasmatic nucleus neurons. Neuron 38: 253-263.