title: Effect of monovalent cations on the kinetics of hypoxic conformational change of mitochondrial complex I.
abstract: 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.
authors.affiliation: Queen's University Belfast, School of Biological Sciences, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK; N.K. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilova Str., Moscow 119334, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Stepanova
authors.affiliation: University of Barcelona, Faculty of Biology, Diagonal, 643, 08028 Barcelona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Valls
authors.affiliation: Queen's University Belfast, School of Biological Sciences, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address: a.galkin@qub.ac.uk.
authors.forename: Alexander
authors.initials: A
authors.lastname: Galkin
keywords: A/D transition; Conformational change; Ischemia/reperfusion; Mitochondrial complex I; NADH:ubiquinone oxidoreductase; Sodium