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Multiple phosphorylations of cytochrome c oxidase and their functions
Author(s) -
Helling Stefan,
Hüttemann Maik,
Ramzan Rabia,
Kim Su Hyeon,
Lee Icksoo,
Müller Thorsten,
Langenfeld Elmar,
Meyer Helmut E.,
Kadenbach Bernhard,
Vogt Sebastian,
Marcus Katrin
Publication year - 2012
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201100618
Subject(s) - allosteric regulation , phosphorylation , protein subunit , cytochrome c oxidase , biochemistry , atp synthase , chemistry , mitochondrion , enzyme , allosteric enzyme , biology , microbiology and biotechnology , gene
Cytochrome c oxidase ( COX ), the terminal enzyme of the mitochondrial electron transport chain, is regulated by isozyme expression, allosteric effectors such as the ATP / ADP ratio, and reversible phosphorylation. Of particular interest is the “allosteric ATP ‐inhibition,” which has been hypothesized to keep the mitochondrial membrane potential at low healthy values (<140 m V ), thus preventing the formation of superoxide radical anions, which have been implicated in multiple degenerative diseases. It has been proposed that the “allosteric ATP ‐inhibition” is switched on by the protein kinase A ‐dependent phosphorylation of COX . The goal of this study was to identify the phosphorylation site(s) involved in the “allosteric ATP ‐inhibition” of COX . We report the mass spectrometric identification of four new phosphorylation sites in bovine heart COX . The identified phosphorylation sites include T yr‐218 in subunit II, S er‐1 in subunit V a, S er‐2 in subunit Vb, and S er‐1 in subunit VIIc. With the exception of S er‐2 in subunit Vb, the identified phosphorylation sites were found in enzyme samples with and without “allosteric ATP inhibition,” making S er‐2 of subunit Vb a candidate site enabling allosteric regulation. We therefore hypothesize that additional phosphorylation(s) may be required for the “allosteric ATP ‐inhibition,” and that these sites may be easily dephosphorylated or difficult to identify by mass spectrometry.