Redox-linked proton translocation by NADH-ubiquinone reductase (complex I).

Abstract

The respiratory chain NADH-ubiquinone reductase (EC 1.6.5.3) of mitochondria, which is also called complex I, links electron transfer from NADH to ubiquinone with translocation of 4 or 5 protons across the inner membrane. The enzyme comprises some 30 different subunits, one FMN, a still not extactly defined number of iron-sulfur clusters, and probabty one form of bound ubiquinone as internal redox groups. It is because of this enormous complexity, that NADH-ubiquinone reductase has remained the least understood among the proton translocating complexes of mitochondria (for reviews see Hatefi, 1985; Ragan, 1987; Weiss et al., 1991). More recent biochemical investigations in combination with electron microscopic studies (Friedrich et al., 1989; Wang et al., 1991; Tuschen et al., 1990; G. Hofhaus, H. Weiss, and K. Leonard, unpublished results) have revealed that complex I is constructed of two distinct parts. They are assembled and probably emerged in evolution independently of each other, are arranged in a different manner with regard to the mitochondrial inner membrane, and contribute distinct segments to the electron pathway in the complex (for review see Weiss et al., 1991). Furthermore, by sequence comparison, related electron transfer segments have been discovered in completely different bacterial enzymes (Friedrich et al., 1990; Pilkington et al., 1991;