tailieunhanh - Báo cáo khoa học: Complementation of coenzyme Q-deficient yeast by coenzyme Q analogues requires the isoprenoid side chain

The ubiquinone coenzyme Q (CoQ) is synthesized in mitochondria with a large, hydrophobic isoprenoid side chain. It functions in mitochondrial res-piration as well as protecting membranes from oxidative damage. Yeast that cannot synthesize CoQ (DCoQ) are viable, but cannot grow on nonfer-mentable carbon sources, unless supplied with ubiquinone. | Complementation of coenzyme Q-deficient yeast by coenzyme Q analogues requires the isoprenoid side chain Andrew M. James1 Helena M. Cocheme1 2 Masatoshi Murai3 Hideto Miyoshi3 and Michael P. Murphy1 1 MedicalResearch CouncilMitochondrialBiology Unit Wellcome Trust MRC Building Cambridge UK 2 Institute of Healthy Ageing and GEE University College London Darwin Building London UK 3 Division of Applied Life Sciences Graduate Schoolof Agriculture Kyoto University Sakyo-ku Kyoto Japan Keywords coenzyme Q diauxic shift mitochondria ubiquinone yeast Correspondence A. M. James MedicalResearch Council MitochondrialBiology Unit Wellcome Trust MRC Building Hills Road Cambridge CB2 0XY UK Fax 44 1223 252905 Tel 44 1223 252903 E-mail aj@ Website http Received 18 December 2009 revised 2 February 2010 accepted 22 February 2010 doi The ubiquinone coenzyme Q CoQ is synthesized in mitochondria with a large hydrophobic isoprenoid side chain. It functions in mitochondrial respiration as well as protecting membranes from oxidative damage. Yeast that cannot synthesize CoQ DCoQ are viable but cannot grow on nonfer-mentable carbon sources unless supplied with ubiquinone. Previously we demonstrated that the isoprenoid side chain of the exogenous ubiquinone was important for growth of a DCoQ strain on the nonfermentable substrate glycerol James AM et al. 2005 J Biol Chem 280 21295-21312 . In the present study we investigated the structural requirements of exogenously supplied CoQ2 for growth on glycerol and found that the first double bond of the initial isoprenoid unit is essential for utilization of respiratory substrates. As CoQ2 analogues that did not complement growth on glycerol supported respiration in isolated mitochondria discrimination does not occur via the respiratory chain complexes. The endogenous form of CoQ in yeast CoQ6 is extremely hydrophobic and transported to mitochondria via the endocytic pathway .