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

• Published in: The Journal of cell biology Vol. 219; no. 4; p. 1
• Main Authors: Abrisch, Robert G, Gumbin, Samantha C, Wisniewski, Brett Taylor, Lackner, Laura L, Voeltz, Gia K
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 06.04.2020
• Subjects: Depolarization; Disruption; Endoplasmic Reticulum - metabolism; Fission; Humans; Membrane potential; Membranes; Metabolism; Mitochondria; Mitochondria - metabolism; Mitochondrial Dynamics; Morphology; Organelles; Steady state; Tumor Cells, Cultured
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201911122

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. Here we show that mitochondrial fission and fusion are spatially coordinated at ER membrane contact sites (MCSs). Multiple measures indicate that the mitochondrial fusion machinery, Mitofusins, accumulate at ER MCSs where fusion occurs. Furthermore, 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.