Fission and fusion machineries converge at ER contact sites to regulate mitochondrial morphology

The steady-state morphology of the mitochondrial network is maintained by a balance of constitutive fission and fusion reactions. Disruption of this steady-state morphology results in either a fragmented or elongated network, both of which are associated with altered metabolic states and disease. How the processes of fission and fusion are balanced by the cell is unclear.

 ER MCSs define the interface between polarized and depolarized segments of mitochondria and can rescue the membrane potential of damaged mitochondria by ER-associated fusion.

Mitochondrial morphology and dynamics are critical to normal cellular function. Mitochondrial morphology is maintained by a balance of constitutive fission and fusion reactions and by dynamic movements that occur along the cytoskeleton.

 How fission and fusion machineries are coordinatedto produce mitochondria of appropriatesize is a fundamentalquestionthat is still unresolved.

the processes of fission and fusion are spatially coordinated and colocalized in a system of ER MCS nodes to regulate mitochondrial shape and health.

The major question that remains is how do ER MCSs contribute to both the fission and fusion of mitochondria?

Future studies will investigate whether the forward and reverse rates could be determined at the ER MCS by the relative recruitment and/or posttranslational modifications of fission and fusion machineries, by small signaling molecules like Ca2+, or by the recruitment of activators or inhibitors of these machineries.