Illustration of the core machinery proteins involved in (A) mitochondrial fission and (B) fusion. The classical model proposes that Mfns contain two transmembrane (TM) domains in between HR1 and HR2 domains. Alternatively, Mfns have been recently demonstrated to have only one TM that lies between the two HR domains. Cysteine residues, sensitive to oxidative stress are located in the C-terminal located in the IMS (only Mfn2 structural domains are represented but this new topology is also applicable to Mfn1). Domains are depicted in different colours. Identified location of post-translational modifications are indicated by P (Phosphorylation), N (S-nitrosylation), S (SUMOylation), G (O-GLcNAcylation), A (Acetylation) or U (Ubiquitination); BSE, bundle signalling elements; CC, coil-coil; GED, GTPase effector domain; HR, heptad repeat; MTS, mitochondrial targeting sequence; NTD, nucleotidyl transferase domains; PH, Pleckstrin homology; PR, Proline rich; RR, repeat regions; TM, transmembrane.