Adv Exp Med Biol. 2026 ;1514
299-330
Mitochondria are considered the central organelle in cellular energy metabolism and an integral platform for signal transduction. Respiratory chain complexes are the most abundant and critical protein machines in mitochondria. Thanks to advancing technologies such as cryo-EM, molecular dynamics simulation, and FRET-based live imaging, though still under hot debate, we have now gained a much deeper insight into the organization, regulation, and functional mechanism of the respiratory chain. Accordingly, developing novel compounds targeting mitochondria is particularly appealing, for mitochondria dysfunction might be the underlying cause of many annoying human diseases, including metabolic syndromes, neurodegenerative diseases, cardiovascular diseases, and tumors.
Keywords: Complex I; Drug discovery; Electron transport chain; Mitochondria; Mitochondrial disorders; Respiratory chain complexes; Signaling; Structural biology; Supercomplexes