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S. cerevisiae coq5 mutants require stabilization of the CoQ‐synthome for rescue by COQ5 homologues (605.13)
Author(s) -
Nguyen Theresa,
Clarke Catherine,
Salviati Leonardo,
Casarin Alberto
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.605.13
Subject(s) - mutant , saccharomyces cerevisiae , yeast , biochemistry , protein subunit , coenzyme q – cytochrome c reductase , biology , gene , biosynthesis , transferase , methyltransferase , enzyme , mitochondrion , methylation , cytochrome c
Coenzyme Q (Ubiquinone or Q) is an essential lipid electron carrier in the respiratory electron chain. In Saccharomyces cerevisiae, eleven genes ( COQ1‐9, ARH1, YAH1 ) are required for coenzyme Q biosynthesis, several of which encode proteins involved in a multi‐subunit complex termed the CoQ‐synthome. One of these genes, COQ5 , encodes a C ‐methyltransferase responsible for making the late stage intermediate demethoxy Q 6 (DMQ 6 ). COQ5 has three conserved methyltransferase motifs, and yeast point mutants within or adjacent to these motifs ( coq5‐2 , coq5‐5 ) lack Coq5 activity but retain steady state levels of the Coq5 polypeptide. We show that the E. coli ubiE and human homologues for COQ5 are able to rescue coq5‐2 and coq5‐5 point mutants, but are unable able to rescue the yeast coq5 Δ null mutant. However when putative kinase Coq8 is over‐expressed to stabilize the CoQ‐synthome, non‐yeast Coq5 homologues are able to rescue the yeast COQ5 knockout. We demonstrate that co‐expression of COQ8 and COQ5 homologues in a coq5 Δ null mutant restores Q 6 levels and supports growth on non‐fermentable carbon sources. By observing the accumulation of Q 6 ‐intermediates in coq5 mutants, we have been able to elucidate steps within a novel Q 6 biosynthetic pathway.