The Complex Dance of Organelles during Mitochondrial Division.

Mitochondria are dynamic organelles that undergo cycles of fission and fusion events depending on cellular requirements. During mitochondrial division, the GTPase dynamin-related protein-1 is recruited to endoplasmic reticulum (ER)-induced mitochondrial constriction sites where it drives fission. However, the events required to complete scission of mitochondrial membranes are not well understood. Here, we emphasize the recently described roles for Golgi-derived phosphatidylinositol 4-phosphate (PI4P)-containing vesicles in the last steps of mitochondrial division. We then propose how trans -Golgi network vesicles at mitochondria–ER contact sites and PI4P generation could mechanistically execute mitochondrial division, by recruiting PI4P effectors and/or the actin nucleation machinery. Finally, we speculate on mechanisms to explain why such a complex dance of different organelles is required to facilitate the remodelling of mitochondrial membranes. TGN vesicles are recruited to mitochondria–ER contacts and mitochondrial fission sites. PI4P generated by the Arf1–PI4KIIIβ axis on TGN vesicles drives mitochondrial division downstream of the recruitment and activity of the main actor of fission, Drp1. TGN vesicles and lysosomes are found at ER-induced mitochondrial constrictions leading to four-way organelle contact sites during mitochondrial membrane remodelling. The molecular mechanisms of how TGN vesicles containing PI4P induce mitochondrial division remain unknown. PI4P directly localized at the OMM or on TGN vesicles could recruit specific effectors that, subsequently, activate cytoskeleton-related machinery required to execute the final scission of mitochondrial membranes. Metabolic flux, particularly active lipid exchange and modification at mitochondria–organelle contact sites could promote specialized microdomains that coordinate complex membrane remodelling events. [ABSTRACT FROM AUTHOR]