The specificity of mitochondrial complex I for ubiquinones

Abstract

We report the first detailed study on the ubiquinone (coenzyme Q; abbreviated to Q) analogue specificity of mitochondrial complex I, NADH:Q reductase, in intact submitochondrial particles. The enzymic function of complex I has been investigated using a series of analogues of Q as electron acceptor substrates for both electron transport activity and the associated generation of membrane potential. Q analogues with a saturated substituent of one to three carbons at position 6 of the 2,3-dimethoxy-5-methyl-1,4-benzoquinone ring have the fastest rates of electron transport activity, and analogues with a substituent of seven to nine carbon atoms have the highest values of association constant derived from NADH:Q reductase activity. The rate of NADH:Q reductase activity is potently but incompletely inhibited by rotenone, and the residual rotenone-insensitive rate is stimulated by Q analogues in different ways depending on the hydrophobicity of their substituent. Membrane potential measurements have been undertaken to evaluate the energetic efficiency of complex I with various Q analogues. Only hydrophobic analogues such as nonyl-Q or undecyl-Q show an efficiency of membrane potential generation equivalent to that of endogenous Q. The less hydrophobic analogues as well as the isoprenoid analogue Q-2 are more efficient as substrates for the redox activity of complex I than for membrane potential generation. Thus the hydrophilic Q analogues act also as electron sinks and interact incompletely with the physiological Q site in complex I that pumps protons and generates membrane potential.

CNS neurons express two distinct plasma membrane electron transport systems implicated in neuronal viability

“…Although stimulation of FeCN reductase activity by exogenous hydrophilic ubiquinone analogs has been previously reported in non-neuronal cells, the relative stimulation in neurons is comparatively greater (Vaillant et al 1996). It is possible that a limiting amount of endogenous ubiquinone is present in the neuronal plasma membranes (Aberg et al 1992) or that the smaller, hydrophilic CoQ 1 is able to interact with redox sites inaccessible to endogenous ubiquinone and thereby mediate more rapid electron transfer between constituents of the redox pathway (Degli Esposti et al 1996).…”

Coenzyme Q1redox metabolism during passage through the rat pulmonary circulation and the effect of hyperoxia

“…Previous studies have addressed the quinone specificity of mitochondrial complex I and NQO1 (1,29,30,33,45,48). Complex I, which catalyzes the transfer of electrons from NADH to ubiquinone, appears to be specific in terms of the structural and steric requirements for quinones to act as good electron acceptors (29,30,45).…”

Structures and Proton-Pumping Strategies of Mitochondrial Respiratory Enzymes

“…Also, the presence of both competitive and noncompetitive inhibition modes for several Complex I inhibitors suggests the presence of two sites (44). Dual binding sites have also been postulated on the basis of the differences in reaction kinetics and proton pumping by various ubiquinone analogs (31). EPR studies of energized submitochondrial particles have shown the presence of two semiquinone radical signals associated with Complex I, one of which is eliminated in the presence of respiratory decouplers.…”