title: Calcium binding and transport by coenzyme Q.
abstract: Coenzyme Q10 (CoQ10) is one of the essential components of the mitochondrial electron-transport chain (ETC) with the primary function to transfer electrons along and protons across the inner mitochondrial membrane (IMM). The concomitant proton gradient across the IMM is essential for the process of oxidative phosphorylation and consequently ATP production. Cytochrome P450 (CYP450) monoxygenase enzymes are known to induce structural changes in a variety of compounds and are expressed in the IMM. However, it is unknown if CYP450 interacts with CoQ10 and how such an interaction would affect mitochondrial function. Using voltammetry, UV-vis spectrometry, electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), fluorescence microscopy and high performance liquid chromatography-mass spectrometry (HPLC-MS), we show that both CoQ10 and its analogue CoQ1, when exposed to CYP450 or alkaline media, undergo structural changes through a complex reaction pathway and form quinone structures with distinct properties. Hereby, one or both methoxy groups at positions 2 and 3 on the quinone ring are replaced by hydroxyl groups in a time-dependent manner. In comparison with the native forms, the electrochemically reduced forms of the new hydroxylated CoQs have higher antioxidative potential and are also now able to bind and transport Ca(2+) across artificial biomimetic membranes. Our results open new perspectives on the physiological importance of CoQ10 and its analogues, not only as electron and proton transporters, but also as potential regulators of mitochondrial Ca(2+) and redox homeostasis.
authors.affiliation: Department of Biophysics, School of Medicine, Saarland University, 66421 Homburg, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bogeski
authors.forename: Rubin
authors.initials: R
authors.lastname: Gulaboski
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kappl
authors.forename: Valentin
authors.initials: V
authors.lastname: Mirceski
authors.forename: Marina
authors.initials: M
authors.lastname: Stefova
authors.forename: Jasmina
authors.initials: J
authors.lastname: Petreska
authors.forename: Markus
authors.initials: M
authors.lastname: Hoth
mesh_terms: D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004563:Electrochemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006900:Hydroxylation; D012972:Sodium Hydroxide / Q000737:chemistry; D013053:Spectrophotometry; D014451:Ubiquinone / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014451:Ubiquinone; D012972:Sodium Hydroxide; D003577:Cytochrome P-450 Enzyme System; D002118:Calcium