Loss of a conserved tyrosine residue of cytochrome b induces reactive oxygen species production by cytochrome bc1

Dong Woo Lee, Nur Selamoglu, Pascal Lanciano, Jason W. Cooley, Isaac Forquer, David M. Kramer, Fevzi Daldal

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Production of reactive oxygen species (ROS) induces oxidative damages, decreases cellular energy conversion efficiencies, and induces metabolic diseases in humans. During respiration, cytochrome bc1 efficiently oxidizes hydroquinone to quinone, buthowit performs this reaction without any leak of electrons to O2 to yield ROS is not understood. Using the bacterial enzyme, here we show that a conserved Tyr residue of the cytochrome b subunit of cytochrome bc1 is critical for this process. Substitution of this residue with other amino acids decreases cytochrome bc1 activity and enhances ROS production. Moreover, the Tyr to Cys mutation cross-links together the cytochrome b and iron-sulfur subunits and renders the bacterial enzyme sensitive to O2 by oxidative disruption of its catalytic [2Fe-2S] cluster. Hence, this Tyr residue is essential in controlling unproductive encounters between O2 and catalytic intermediates at the quinol oxidation site of cytochrome bc1 to prevent ROS generation. Remarkably, the same Tyr to Cys mutation is encountered in humans with mitochondrial disorders and in Plasmodium species that are resistant to the anti-malarial drug atovaquone. These findings illustrate the harmful consequences of this mutation in human diseases.

Original languageEnglish
Pages (from-to)18139-18148
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number20
DOIs
Publication statusPublished - 2011 May 20

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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