ER-associated mitochondrial fission and fusion

The steady-state morphology of the mitochondrial network is maintained by a balance of 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. However, we have shown that mitochondrial fission and fusion are spatially coordinated at ER membrane contact sites (MCSs). Multiple measures indicate that both mitochondrial fission and fusion machineries colocalize to form hotspots for membrane dynamics at ER MCSs that can persist through sequential events. Because these hotspots can undergo fission and fusion, they have the potential to quickly respond to metabolic cues. Indeed, we discover that 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. Our current goal is to identify how ER associated nodes are assembled, how the activities of the fission and fusion machineries are balanced, and by what mechanism do ER proteins drive mitochondrial constriction to form fission and fusion hotspots.

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Electron tomography reveals the three-dimensional structure of MCSs (coloured red) between ER tubules (green) and mitochondria (purple) in a yeast cell (right) or an endosome (yellow) in an animal cell (left). EM Tomography done by Matthew West.

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