Cytochrome bc1 complex (Mitochondrial Complex III) (Complex III)

Mitochondrial Complex III, also known as the cytochrome bc1 complex, is a central component of the electron transport chain responsible for transferring electrons from ubiquinol to cytochrome c [16, 18]. This process is coupled to proton translocation across the inner mitochondrial membrane, creating the electrochemical gradient necessary for ATP synthesis via the Q-cycle [16]. The complex contains two distinct quinone-binding sites: the Qo site (outer, ubiquinol oxidation) and the Qi site (inner, ubiquinone reduction) [18]. These sites are critical therapeutic targets; for instance, the Qo site is targeted by the antimalarial drug atovaquone, while the Qi site is inhibited by compounds like antimycin A [1, 3, 6]. Beyond energy production, Complex III is a major source of cellular reactive oxygen species (ROS) and plays a key role in hypoxic signaling through the stabilization of HIF-1alpha [19, 22]. Dysregulation or inhibition of these sites is linked to various conditions, including parasitic infections, mitochondrial myopathies, and cancer progression [6, 10, 12]. In parasites like Plasmodium, inhibition of this complex also disrupts pyrimidine biosynthesis, which is essential for survival [13].

Other names

Ubiquinol-cytochrome c reductaseCoenzyme Q-cytochrome c reductasebc1 complexQo siteQi siteUbiquinol oxidation siteUbiquinone reduction site

Inhibition of the Q-cycle by binding to the Qo or Qi sites, blocking electron transfer from ubiquinol to cytochrome c [16]. This disruption halts the generation of the proton motive force required for ATP synthesis and leads to the accumulation of electrons on upstream carriers, promoting the generation of reactive oxygen species (ROS) such as superoxide [1, 4, 21].