Molecular Mechanism Of Mitochondrial Lateral Fusion

Mitochondria is often in the dynamic state of continuous fusion and division in the cell.The continuous fusion and fission of mitochondria ensures the mixture of DNA between mitochondria and the normal functioning of mitochondrial metabolism.Mitochondrial fusion event is regulated by a group of dynamin-like GTPases.So far,the studies in this field have shown that genetic mutation of these genes cause invariably hereditary neurodegenerative disease.Syntabulin plays an important role in the vesicle and mitochondrial transport of neuronal axons.Our recent study shown that syntabulin also have the effect of inducing mitochondrial fusion,but the mechanism is unclear.In this paper,we have studied the mechanisms of syntabulin-induced mitochondrial fusion,by using the techniques of molecular cloning,in vitro expression,gene silencing,dynamic observation of molecular and subcellular image,Co-immunoprecipitation and other techniques.We found that syntabulin could induce mitochondria fusion on the microtubule platform and form a long tubular network structure by not only increasing the mitochondrial top contacting,but also by promoting mitochondrial lateral connection and vertical contacting.Through the interaction coiled-coil domainbetween syntabulin molecules,two mitochondria were arranged in parallel along their long axis and perpendicular connected at their crossing site to induce mitochondrial lateral fusion and branching.When the microtubules were depolymerized,tubular mitochondrial networks were also disrupted.Short rod-shaped mitochondria were assembled into a lateral arrangement of a special structure by syntabulin.A number of mitochondria packed into a complex structure that was connected by stair-step like arranged syntabulin..In a few cells,we can see long tubular mitochondria were adhered to form a double tubular structure.Through the experiments of live cells imaging we confirmed that mitochondrial could be lateral and vertical fusion in primary nerve cells which were natural expressing syntabulin.Therefore,syntabulin regulates the mitochondrial fusion in a new way of promoting the lateral interaction between mitochondria and mediates theformation of mitochondrial network on the platform of microtubule.Dynamin GTPase like molecules are generally required in the process of mitochondrial fusion.In our studies,we found that mitochondrial Rho GTPase could interact with the syntabulin.it may participate in the mitochondrial fusion process mediated by syntabulin..In conclusion,this study found a new mitochondrial fusion regulatory system for the first time other than Dynamin's GTPase,in which the core components are composed of syntabulin,microtubules and mitochondrial Rho GTPase Miro.This will be an important alternative system for the regulation of mitochondrial fusion events.