Flavoproteins of the electron transport system and the site of action of amytal, rotenone, and piericidin A.

Previous studies1-4 have shown that the mitochondrial electron transport system can be divided into four enzyme complexes: DPNH-coenzyme Q reductase (complex I)," succinate-coenzyme Q reductase (complex II), reduced coenzyme Q-cyt. c reductase (complex I), and cyt. c oxidase (complex IV). When mixed together in the presence of cyt. c, these complexes recombined in the sequence and the approximate ratio of components found in intact mitochondria, and thus reconstituted a particulate unit with all the apparent catalytic and inhibitorresponse properties of intact electron transfer particles (ETP). On the basis of these findings, the tentative structure shown in Figure 1 was proposed for the electron transport system. Subsequently, it was shown4 that complex I could be resolved into three fractions: a DPNH dehydrogenase ferroflavoprotein (FP) (mol wt 70,000) containing FMN, iron, and labile sulfide in an approximate ratio of 1:4:4; an iron-sulfur protein (IP) containing equimolar amounts of iron and labile sulfide but no flavin; and a third protein fraction with properties similar to the mitochondrial "structural" proteins. Moreover, it was demonstrated that electron transfer between the resolved components of complex I can occur as shown in reaction (1):