PARENT SESSION
Posters P8A Cytochrome b-c complexes. Abstracts (382-393)

Mechanistic and physiological significance of superoxide production at the Qo-site of the yeast cytochrome bc₁-complex. Atsuko Kanazawa^*,1, Florian Muller¹, David Kramer¹, ¹ Institute of Biological Chemistry, Pullman, Washington, USA

ABSTRACT- We are developing a system to assess the mechanistic and physiological importance of superoxide (SO) production by the cytochrome (cyt) bc₁ complex based on yeast (Saccharomyces cerevisiae). At stationary phase, yeast is very sensitive to SO, and this condition is considered to be comparable to the aging problem in the mammalian cells. The proximal Qo-site inhibitors such as myxothiazol, mucidine, MOA-stilbene, and famoxadone, and the Qi-site inhibitor, Antimycin A, induced production of SO both in vitro (as probed by chemical assays) and in vivo (as probed by the effects on cell viability). A mutant line lacking the cytosolic superoxide dismutase was considerably more sensitive to increased SO production, while inhibitors of electron transfer, e.g. KCN, which will prevent SO-producing partial turnover of the cyt bc1 complex ameliorated the effects. We propose a model wherein any conditions which specifically inhibits electron transfer from the Qo-site semiquinone to cyt b_L will increase SO production. We are currently exploiting this new system to test the mechanisms of SO production at the Qo-site under more physiological conditions, as influenced by mitochondrial mutations.

KEY WORDS: superoxide, bc1 complex, Q-cycle, yeast