The nuclear ABC1 gene is essential for the correct conformation and functioning of the cytochrome bc(1) complex and the neighbouring complexes II and IV in the mitochondrial respiratory chain

The nuclear ABC1 gene was isolated as a multicopy suppressor of a cytochrome b mRNA translation defect. Its inactivation leads to a respiratory deficiency suggesting a block in the bc(1) segment of the respiratory chain [Bousquet, I., Dujardin, G. & Slonimski, P. P. (1991) EMBO J. 10, 2023-2031]. In the present study, we established that deleting the ABC1 chromosomal gene from Saccharomyces cerevisiae does not prevent the assembly of the bc(1) complex (complex III) but markedly impairs the kinetics of its high-potential electron transfer pathway occurring on the positive, outer, side of the membrane, which results in reduced activity of the bc(1) complex. In addition, the activity of complex II and its cytochrome b(560) decrease drastically and complex IV activity is halved. It is also observed that the binding of the quinol to the bc(1) complex ubiquinol oxidation site is affected and that adding exogenous quinones partially compensates for the respiratory deficiency in vitro, although the quinone content of mutant and wild-type mitochondria are similar. Lastly, complexes II, III and IV are found to be thermosensitive and the bc(1) complex exhibits greater sensitivity than the wild-type strain to center N and P inhibitors, suggesting that the three multisubunit complexes have undergone structural modifications. The data suggest that the ABC1 gene product acts as a chaperone-like protein essential for the proper conformation and efficient functioning of the bc(1) complex and the effects of the Abc1 protein on the complexes II and IV might result from interactions with the modified bc(1) complex.