Regulation of coenzyme Q biosynthesis in yeast: a new complex in the block.
Coenzyme Q (CoQ) is an isoprenylated benzoquinone found in mitochondria, which functions mainly as an electron carrier from complex I or II to complex III in the inner membrane. CoQ is also an antioxidant that specifically prevents the oxidation of lipoproteins and the plasma membrane. Most of the information about the synthesis of CoQ comes from studies performed in Saccharomyces cerevisiae. CoQ biosynthesis is a highly regulated process of sequential modifications of the benzene ring. There are three pieces of evidence supporting the involvement of a multienzymatic complex in yeast CoQ6 biosynthesis: (a) the accumulation of a unique early precursor in all null mutants of the COQ genes series, 4-hydroxy-3-hexaprenyl benzoate (HHB), (b) the lack of expression of several Coq proteins in COQ null mutants, and (c) the restoration of CoQ biosynthesis complex after COQ8 overexpression. The model we propose based on the formation of a multiprotein complex should facilitate a better understanding of CoQ biosynthesis. According to this model, the complex assembly requires the synthesis of a precursor such as HHB by Coq2p that must be recognized by the regulatory protein Coq4p to act as the core component of the complex. The phosphorylation of Coq3p and Coq5p by the kinase Coq8p facilitates the formation of an initial precomplex of 700 kDa that contains all Coq proteins with the exception of Coq7p. The precomplex is required for the synthesis of 5-demethoxy-Q6 , the substrate of Coq7p. When cells require de novo CoQ6 synthesis, Coq7p is dephosphorylated by Ptc7p, a mitochondrial phosphatase that activates the synthesis of CoQ6. This event allows for the full assembly of a complex of 1,300 kDa that is responsible for the final product of the pathway, CoQ6 .
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide-CSIC, CIBERER Instituto de Salud Carlos III, Sevilla, Spain.
Isabel
I
González-Mariscal
Elena
E
García-Testón
Sergio
S
Padilla
Alejandro
A
Martín-Montalvo
Teresa
T
Pomares-Viciana
Luis
L
Vazquez-Fonseca
Pablo
P
Gandolfo-Domínguez
Carlos
C
Santos-Ocaña
D000975:Antioxidants / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics*; D051336:Mitochondrial Membranes / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D014451:Ubiquinone / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; C032165:ubiquinone 6; D014451:Ubiquinone
coenzyme Q; mitochondria; mitochondrial complex; phosphatase; phosphoprotein; respiration; ubiquinone