Effect of monovalent cations on the kinetics of hypoxic conformational change of mitochondrial complex i

Anna Stepanova, Alba Valls, Alexander Galkin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
230 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)1085-1092
Number of pages8
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1847
Issue number10
Early online date22 May 2015
DOIs
Publication statusPublished - Oct 2015

Keywords

  • A/D transition
  • Conformational change
  • Ischemia/reperfusion
  • Mitochondrial complex I
  • NADH:ubiquinone oxidoreductase
  • Sodium

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology

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