Effect of monovalent cations on the kinetics of hypoxic conformational change of mitochondrial complex I
| Autor: | Alba Valls, Alexander Galkin, Anna Stepanova |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Conformational change
Q1 2 3-dimethoxy-5-methyl-6-(3-methyl-2-butenyl)-1 4-benzoquinone Sodium Kinetics FCCP carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone Biophysics Ischemia/reperfusion chemistry.chemical_element Mitochondrial complex I Stimulation Biochemistry Article A/D active/de-active transition NADH:ubiquinone oxidoreductase 03 medical and health sciences ROS reactive oxygen species In vivo 030304 developmental biology chemistry.chemical_classification 0303 health sciences ubiquinone oxidoreductase [NADH] 030302 biochemistry & molecular biology Cell Biology Alkali metal Enzyme chemistry Ionic strength EIPA 5-(N-Ethyl-N-isopropyl)amiloride SMP bovine heart submitochondrial particles TMH transmembrane helix BSA bovine serum albumin A/D transition HAR hexaammineruthenium(III)-chloride |
| Zdroj: | Stepanova, A, Valls, A & Galkin, A 2015, ' Effect of monovalent cations on the kinetics of hypoxic conformational change of mitochondrial complex i ', Biochimica et Biophysica Acta-Bioenergetics, vol. 1847, no. 10, pp. 1085-1092 . https://doi.org/10.1016/j.bbabio.2015.05.012 Biochimica et Biophysica Acta |
| ISSN: | 0005-2728 |
| DOI: | 10.1016/j.bbabio.2015.05.012 |
| Popis: | Mitochondrial complex I is a large, membrane-bound enzyme central to energy metabolism, and its dysfunction is implicated in cardiovascular and neurodegenerative diseases. An interesting feature of mammalian complex I is the so-called A/D transition, when the idle enzyme spontaneously converts from the active (A) to the de-active, dormant (D) form. The A/D transition plays an important role in tissue response to ischemia and rate of the conversion can be a crucial factor determining outcome of ischemia/reperfusion. Here, we describe the effects of alkali cations on the rate of the D-to-A transition to define whether A/D conversion may be regulated by sodium. At neutral pH (7–7.5) sodium resulted in a clear increase of rates of activation (D-to-A conversion) while other cations had minor effects. The stimulating effect of sodium in this pH range was not caused by an increase in ionic strength. EIPA, an inhibitor of Na+/H+ antiporters, decreased the rate of D-to-A conversion and sodium partially eliminated this effect of EIPA. At higher pH (> 8.0), acceleration of the D-to-A conversion by sodium was abolished, and all tested cations decreased the rate of activation, probably due to the effect of ionic strength. The implications of this finding for the mechanism of complex I energy transduction and possible physiological importance of sodium stimulation of the D-to-A conversion at pathophysiological conditions in vivo are discussed. Highlights • The active/dormant (A/D) transition of complex I is affected by monovalent cations. • Na+ increases the rate of the D/A conversion at neutral pH. • Lithium and caesium decrease D/A transition at all tested pH • Matrix ion balance may influence the rate of the activation of the enzyme in situ. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect