Mitochondrial electron transport chain (METC) and cellular redox machinery (METC)

The cellular redox machinery and mitochondrial electron transport chain (ETC) constitute the primary bioenergetic and homeostatic system of the cell, responsible for generating ATP and maintaining oxidative balance [1.3.1]. The ETC, located in the inner mitochondrial membrane, consists of five multi-subunit complexes (I-V) that facilitate electron transfer and proton pumping to drive oxidative phosphorylation [1.3.5]. This process is intrinsically linked to the cellular redox machinery, which includes the glutathione and thioredoxin systems, to neutralize reactive oxygen species (ROS) produced as metabolic byproducts [1.1.4]. In diseases like cancer, these systems are often reprogrammed to support rapid proliferation and survival under stress, making them attractive therapeutic targets for a class of drugs known as mitocans [1.2.1]. Drugs such as elesclomol exploit these vulnerabilities by disrupting electron flow to induce lethal ROS levels [1.2.3]. Conversely, in neurodegenerative and cardiovascular diseases, therapeutic strategies often aim to stabilize or bypass dysfunctional ETC components to reduce oxidative damage and restore energy balance [1.2.2, 1.3.3].

Other names

Mitochondrial respiratory chainOxidative phosphorylation systemOXPHOSCellular antioxidant systemRedox homeostasis machinery

Drugs targeting this system typically inhibit specific complexes of the mitochondrial electron transport chain (e.g., Complex I inhibition by metformin or rotenone) or disrupt the cellular redox balance by inhibiting antioxidant enzymes such as thioredoxin reductase (e.g., auranofin) or glutathione synthesis (e.g., buthionine sulfoximine) [1.1.1, 1.2.3, 1.3.2]. These actions lead to the accumulation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and the induction of apoptosis, particularly in cancer cells which often exhibit altered mitochondrial metabolism [1.2.1, 1.2.5].