Gellerich 2013 Abstract MiP2013

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

1. Korzeniewski B (2007) Regulation of oxidative phosphorylation through parallel activation. Biophys Chem 129: 93-110.
2. 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.
3. 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..
4. 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.
5. 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.
6. 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.
7. Satrústegui J, Pardo B, Del Arco A. (2007) Mitochondrial transporters as novel targets for intracellular calcium signaling. Physiol Rev 87: 29-67.
8. 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.