The redox-Bohr group associated with iron-sulfur cluster N2 of complex I

K. Zwicker, Alexander Galkin, S. Drose, L. Grgic, S. Kerscher, U. Brandt

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

Proton pumping respiratory complex I (NADH: ubiquinone oxidoreductase) is a major component of the oxidative phosphorylation system in mitochondria and many bacteria. In mammalian cells it provides 40% of the proton motive force needed to make ATP. Defects in this giant and most complicated membrane-bound enzyme cause numerous human disorders. Yet the mechanism of complex I is still elusive. A group exhibiting redox-linked protonation that is associated with iron-sulfur cluster N2 of complex I has been proposed to act as a central component of the proton pumping machinery. Here we show that a histidine in the 49-kDa subunit that resides near iron-sulfur cluster N2 confers this redox-Bohr effect. Mutating this residue to methionine in complex I from Yarrowia lipolytica resulted in a marked shift of the redox midpoint potential of iron-sulfur cluster N2 to the negative and abolished the redox-Bohr effect. However, the mutation did not significantly affect the catalytic activity of complex I and protons were pumped with an unchanged stoichiometry of 4 H+/2e(-). This finding has significant implications on the discussion about possible proton pumping mechanism for complex I.
Original languageEnglish
Pages (from-to)23013-23017
Number of pages5
JournalJournal of Biological Chemistry
Volume281
Issue number32
DOIs
Publication statusPublished - 11 Aug 2006

ASJC Scopus subject areas

  • Biochemistry

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