Regulation and functional role of the electron transport chain supercomplexes

Mitochondria are one of the most exhaustively investigated organelles in the cell and most attention has been paid to the components of the mitochondrial electron transport chain (ETC) in the last 100 years. The ETC collects electrons from NADH or FADH2 and transfers them through a series of electron carriers within multiprotein respiratory complexes (complex I to IV) to oxygen, therefore generating an electrochemical gradient that can be used by the F1-F0-ATP synthase (also named complex V) in the mitochondrial inner membrane to synthesize ATP. The organization and function of the ETC is a continuous source of surprises. One of the latest is the discovery that the respiratory complexes can assemble to form a variety of larger structures called super-complexes (SCs). This opened an unexpected level of complexity in this well-known and fundamental biological process. This review will focus on the current evidence for the formation of different SCs and will explore how they modulate the ETC organization according to the metabolic state. Since the field is rapidly growing, we also comment on the experimental techniques used to describe these SC and hope that this overview may inspire new technologies that will help to advance the fieldMINECO: SAF2015-65633-R, MCIU: RTI2018-099357-B-I00, CIBERFES (CB16/10/00282) and HFSP (RGP0016/2018). The CNIC is supported by the Ministry Science and Innovation (MSI) and the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (MSI award SEV-2015-0505