ubiquinone-9 and ubiquinone-7

Coenzyme Q (CoQ) is a redox-active lipid essential for core metabolic pathways and antioxidant defense. CoQ is synthesized upon the mitochondrial inner membrane by an ill-defined "complex Q" metabolon. Here, we present structure-function analyses of a lipid-, substrate-, and NADH-bound complex comprising two complex Q subunits: the hydroxylase COQ7 and the lipid-binding protein COQ9. We reveal that COQ7 adopts a ferritin-like fold with a hydrophobic channel whose substrate-binding capacity is enhanced by COQ9. Using molecular dynamics, we further show that two COQ7:COQ9 heterodimers form a curved tetramer that deforms the membrane, potentially opening a pathway for the CoQ intermediates to translocate from the bilayer to the proteins' lipid-binding sites. Two such tetramers assemble into a soluble octamer with a pseudo-bilayer of lipids captured within. Together, these observations indicate that COQ7 and COQ9 cooperate to access hydrophobic precursors within the membrane and coordinate subsequent synthesis steps toward producing CoQ.

Topics: Carrier Proteins; Humans; Lipids; Mitochondrial Membranes; Ubiquinone

We studied ubiquinone (Q), Q homologue ratio, and steady-state levels of mCOQ transcripts in tissues from mice fed ad libitum or under calorie restriction. Maximum ubiquinone levels on a protein basis were found in kidney and heart, followed by liver, brain, and skeletal muscle. Liver and skeletal muscle showed the highest Q(9)/Q(10) ratios with significant interindividual variability. Heart, kidney, and particularly brain exhibited lower Q(9)/Q(10) ratios and interindividual variability. In skeletal muscle and heart, the most abundant mCOQ transcript was mCOQ7, followed by mCOQ8, mCOQ2, mPDSS2, mPDSS1, and mCOQ3. In nonmuscular tissues (liver, kidney, and brain) the most abundant mCOQ transcript was mCOQ2, followed by mCOQ7, mCOQ8, mPDSS1, mPDSS2, and mCOQ3. Calorie restriction increased both ubiquinone homologues and mPDSS2 mRNA in skeletal muscle, but mCOQ7 was decreased. In contrast, Q(9) and most mCOQ transcripts were decreased in heart. Calorie restriction also modified the Q(9)/Q(10) ratio, which was increased in kidney and decreased in heart without alterations in mPDSS1 or mPDSS2 transcripts. We demonstrate for the first time that unique patterns of mCOQ transcripts exist in muscular and nonmuscular tissues and that Q and COQ genes are targets of calorie restriction in a tissue-specific way.

Topics: Animals; Brain; Caloric Restriction; Free Radicals; Kidney; Liver; Mice; Muscle, Skeletal; Myocardium; Organ Specificity; RNA, Messenger; Ubiquinone

The thermotropic properties of coenzymes Q10, Q9, Q8, and Q7 have been examined by differential scanning calorimetry and wide-angle X-ray diffraction. Typical scanning calorimetry cooling curves of coenzyme Q from the liquid state exhibit a single exothermic phase transition into a crystalline state at a temperature that decreases as the length of the polyisoprenoid side-chain substituent decreases. Upon subsequent heating, the molecules undergo a series of thermal events which precede the main crystalline-to-liquid endothermic phase transition. The temperature of these transitions increases with increasing chain length. The crystallization phase transition temperature depends markedly on the rate at which the sample is cooled and increases with decreasing scan rate; the temperature of the melting endotherm is not markedly affected by the scan rate. Detailed calorimetric studies of coenzyme Q10 indicate that two crystalline states are formed, one at relatively high cooling rates to low temperatures and the other when preparations are cooled slowly from the liquid state to relatively high temperatures. Heating the crystalline phase formed by rapid cooling causes its transformation into the phase observed by cooling slowly. X-ray diffraction analysis confirmed the existence of these two crystal phases in coenzymes Q9 and Q10 and the transformation from the rapidly crystallized form to the more ordered form associated with slower cooling rates. At body temperature (310 K) under equilibrium conditions coenzyme Q10 exists in an ordered crystalline phase; the implications of the thermotropic behavior of coenzyme Q10 on mitochondrial function in vitro and in vivo are discussed.

Topics: Calorimetry, Differential Scanning; Coenzymes; Crystallization; Crystallography, X-Ray; Mitochondria; Thermodynamics; Ubiquinone

Topics: Animals; Anti-Infective Agents; Coenzymes; Female; Immunity, Cellular; Listeriosis; Mice; Spleen; Ubiquinone