The role of Sdh4p Tyr-89 in ubiquinone reduction by the Saccharomyces cerevisiae succinate dehydrogenase.
Succinate dehydrogenase (complex II or succinate:ubiquinone oxidoreductase) is a tetrameric, membrane-bound enzyme that catalyzes the oxidation of succinate and the reduction of ubiquinone in the mitochondrial respiratory chain. Two electrons from succinate are transferred one at a time through a flavin cofactor and a chain of iron-sulfur clusters to reduce ubiquinone to an ubisemiquinone intermediate and to ubiquinol. Residues that form the proximal quinone-binding site (Q(P)) must recognize ubiquinone, stabilize the ubisemiquinone intermediate, and protonate the ubiquinone to ubiquinol, while minimizing the production of reactive oxygen species. We have investigated the role of the yeast Sdh4p Tyr-89, which forms a hydrogen bond with ubiquinone in the Q(P) site. This tyrosine residue is conserved in all succinate:ubiquinone oxidoreductases studied to date. In the human SDH, mutation of this tyrosine to cysteine results in paraganglioma, tumors of the parasympathetic ganglia in the head and neck. We demonstrate that Tyr-89 is essential for ubiquinone reductase activity and that mutation of Tyr-89 to other residues does not increase the production of reactive oxygen species. Our results support a role for Tyr-89 in the protonation of ubiquinone and argue that the generation of reactive oxygen species is not causative of tumor formation.
Silkin
Yuri
Y
Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
Oyedotun
Kayode S
KS
Lemire
Bernard D
BD
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D042963:Electron Transport Complex II / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010235:Paraganglioma / Q000235:genetics; D010673:Pheochromocytoma / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D014443:Tyrosine / Q000235:genetics / Q000502:physiology*; D014451:Ubiquinone / Q000378:metabolism*
D017382:Reactive Oxygen Species; D014451:Ubiquinone; D014443:Tyrosine; D042963:Electron Transport Complex II