Clarifying the supercomplex: the higher-order organization of the mitochondrial electron transport chain

The oxidative phosphorylation electron transport chain (OXPHOS-ETC) of the inner mitochondrial membrane is composed of five large protein complexes, named CI-CV. These complexes convert energy from the food we eat into ATP, a small molecule used to power a multitude of essential reactions throughout the cell. OXPHOS-ETC complexes are organized into supercomplexes (SCs) of defined stoichiometry: CI forms a supercomplex with CIII₂ and CIV (SC I+III₂+IV, known as the respirasome), as well as with CIII₂ alone (SC I+III₂). CIII₂ forms a supercomplex with CIV (SC III₂+IV) and CV forms dimers (CV₂). Recent cryo-EM studies have revealed the structures of SC I+III₂+IV and SC I+III₂. Furthermore, recent work has shed light on the assembly and function of the SCs. Here we review and compare these recent studies and discuss how they have advanced our understanding of mitochondrial electron transport.