The interaction between OPA1 and CL on either side of the membrane tethers the two IMM, which fuse following OPA1-depedent GTP hydrolysis (5). (4) Following OMM fusion, OPA1 and CL drive IMM fusion. The composition of the OMM in phospholipids can also regulate this process. (3) Finally, GTPase-dependent power stroke or GTP-dependent oligomerization ensure OMM fusion. For clarity reasons, not all of the recent suggested models leading to Mfns dimerization and conformational change are highlighted in the scheme. GTP binding or/and hydrolysis induce Mfns conformational change leading to mitochondrial docking and to an increase of membrane contact sites. (1) The outer membrane of two opposing mitochondria are tethered by the interaction in trans of the HR2 and/or GTPase domains of Mfns. ( A) Schematic representations of mitochondrial fusion, based on the Mfns topology suggesting two TM domains with both the HR1 and HR2 domains facing the cytosol. 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. Domains are depicted in different colours. 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). Alternatively, Mfns have been recently demonstrated to have only one TM that lies between the two HR domains. The classical model proposes that Mfns contain two transmembrane (TM) domains in between HR1 and HR2 domains. Illustration of the core machinery proteins involved in ( A) mitochondrial fission and ( B) fusion. This article will describe an overview of the molecular mechanisms that govern mitochondrial fission and fusion in mammals.ĭynamin family ER-Actin Mitochondrial dynamics Molecular Mechanisms Regulation. Understanding the molecular mechanisms controlling mitochondrial dynamics is crucial to decipher how mitochondrial shape meets the function and to increase the knowledge on the molecular basis of diseases associated with morphology defects.
![musikimia biology and mitochondria musikimia biology and mitochondria](https://i1.rgstatic.net/ii/profile.image/766325039308802-1559717535808_Q64/Lea-Dietrich.jpg)
In addition to the role of membrane lipid composition, several members of the machinery can undergo post-translational modifications modulating these processes.
![musikimia biology and mitochondria musikimia biology and mitochondria](http://www.biology4kids.com/files/art/cell_mitochondria1.png)
Mitochondrial fusion is driven by a two-step process with the outer mitochondrial membrane fusion mediated by mitofusins 1 and 2 followed by inner membrane fusion, mediated by optic atrophy 1. Inner mitochondrial membrane constriction has been proposed to be an independent process regulated by calcium influx.
![musikimia biology and mitochondria musikimia biology and mitochondria](https://www.plymouth.ac.uk/uploads/production/media_asset/file/28/28683/medium_Mitochondrial-Biology.jpg)
Drp1 oligomerization followed by mitochondrial constriction leads to the recruitment of Dynamin 2 to terminate membrane scission. It is regulated by the recruitment of the GTPase Dynamin-related protein 1 (Drp1) by adaptors at actin- and endoplasmic reticulum-mediated mitochondrial constriction sites. Mitochondrial fission is a multi-step process allowing the division of one mitochondrion in two daughter mitochondria. These dynamic transitions are mainly ensured by large GTPases belonging to the Dynamin family. Mutations in the core machinery components and defects in mitochondrial dynamics have been associated with numerous human diseases. Their transient and rapid morphological adaptations are crucial for many cellular processes such as cell cycle, immunity, apoptosis and mitochondrial quality control. Mitochondria are highly dynamic organelles undergoing coordinated cycles of fission and fusion, referred as 'mitochondrial dynamics', in order to maintain their shape, distribution and size.