Mitochondrial fission is essential for distributing cellular energy throughout cells and for isolating damaged regions of the organelle that are targeted for degradation. Excessive fission is associated with the progression of cell death as well. Therefore, this multistep process is tightly regulated and several physiologic cues directly impact mitochondrial division. The double membrane structure of mitochondria complicates this process, and protein factors that drive membrane scission need to coordinate the separation of both the outer and inner mitochondrial membranes. In this review, we discuss studies that characterize distinct morphological changes associated with mitochondrial division. Specifically, coordinated partitioning and pinching of mitochondria have been identified as alternative mechanisms associated with fission. Additionally, we highlight the major protein constituents that drive mitochondrial fission and the role of connections with the endoplasmic reticulum in establishing sites of membrane division. Collectively, we review decades of research that worked to define the molecular framework of mitochondrial fission. Ongoing studies will continue to sort through the complex network of interactions that drive this critical event.
Keywords: inter-organelle contacts; mitochondria; mitochondrial dynamics; mitochondrial fission and fusion; morphology.