Hydroxylation of demethoxy-Q6 constitutes a control point in yeast coenzyme Q6 biosynthesis.
Coenzyme Q is a lipid molecule required for respiration and antioxidant protection. Q biosynthesis in Saccharomyces cerevisiae requires nine proteins (Coq1p-Coq9p). We demonstrate in this study that Q levels are modulated during growth by its conversion from demethoxy-Q (DMQ), a late intermediate. Similar conversion was produced when cells were subjected to oxidative stress conditions. Changes in Q(6)/DMQ(6) ratio were accompanied by changes in COQ7 gene mRNA levels encoding the protein responsible for the DMQ hydroxylation, the penultimate step in Q biosynthesis pathway. Yeast coq null mutant failed to accumulate any Q late biosynthetic intermediate. However, in coq7 mutants the addition of exogenous Q produces the DMQ synthesis. Similar effect was produced by over-expressing ABC1/COQ8. These results support the existence of a biosynthetic complex that allows the DMQ(6) accumulation and suggest that Coq7p is a control point for the Q biosynthesis regulation in yeast.
Padilla
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Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC and Centre for Biomedical Research on Rare Diseases (CIBERER), Carretera de Utrera, km 1, ISCIII, 41013 Sevilla, Spain.
Tran
U C
UC
Jiménez-Hidalgo
M
M
López-Martín
J M
JM
Martín-Montalvo
A
A
Clarke
C F
CF
Navas
P
P
Santos-Ocaña
C
C
D006900:Hydroxylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress; D012331:RNA, Fungal / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014451:Ubiquinone / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology
C433869:COQ4 protein, S cerevisiae; C099891:COQ8 protein, S cerevisiae; D024101:Mitochondrial Proteins; D012331:RNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; C032165:ubiquinone 6; D014451:Ubiquinone; C105459:COQ5 protein, S cerevisiae; D008780:Methyltransferases; C070696:3,4-dihydroxy-5-hexaprenylbenzoate methyltransferase; C030777:ubiquinone 7