The Hemifusome: A Brand New Organelle

Earlier this year, a new organelle, the hemifusome, was discovered by researchers at the National Institute of Health (NIH), and the University of Virginia School of Medicine (UVA). The team was co-led by Seham Ebrahim, PhD, assistant professor in the Department of Molecular Physiology and Biological Physics at UVA, and Bechara Kachar, MD, chief of the Laboratory of Cell Structure and Dynamics at the NIH’s National Institute on Deafness and Other Communication Disorders (NIDCD). 

Researchers observed pairs of vesicles, small sacs formed from a membrane, fusing together in ways not seen in other organelles, leading to the discovery of hemifusomes. They most likely form through hemifusion, which is partial fusion of two membranes, hence the name hemifusome. Hemifusomes are estimated to represent 10% of membrane bound organelles, and are thought to be common components of the cell periphery in a wide range of cells and tissues. They are most likely involved in lipid transfer and lipid sorting, an important aspect of a recently discovered pathway for forming multivesicular bodies (MVBs). MVBs are crucial to the sorting and removal of proteins within the cell. It was previously believed that nearly all MVBs were formed through protein scaffolding, which is a specific type of protein that assembles other proteins into their functional form. However, the discovery of hemifusomes provides even more evidence for the new lipid-based formation pathway. 

Previously, this organelle was completely unknown, but it was visualized for the first time in four mammalian cell lines using cryo-electron tomography, which is state-of-the-art electron microscopy technology at the Molecular Electron Microscopy Core (MEMC) facility. Though similar to other vesicle organelles such as lysosomes and endosomes, which are involved in the recycling and breakdown of cells and cellular components, hemifusomes are thought to be a new organelle largely due to their unique configuration, as well as their involvement in the lipid-based formation pathway of MVBs. Hemifusomes can appear in two different configurations: direct, where the smaller vesicle is on the cytoplasmic, or outer, side of the membrane, or flipped, where the smaller vesicle is on the luminal, or inner, side of the membrane.

These findings are not yet peer reviewed, but they are an exciting addition to research regarding vesicles and material transport in cells. As they continue their research, the team acknowledges other potential hypotheses stating that hemifusomes are not a new organelle but rather an intermediate or member of the broader endo-lysosomal system, which includes the lysosome and endosome organelles. However, their current findings led them to believe it is in fact a new organelle. The team will continue to do additional research on the formation of hemifusomes, as this could help clarify its status as an organelle. It is currently believed that they form through hemifusion. This compelling research has the potential to help scientists better understand movement of materials within the cell, as well as diseases related to this process such as Alzheimer’s and certain cancers. Overall, hemifusomes are a fascinating addition to the catalog of organelles, with exciting potential to stir further research and lead to new discoveries across many areas of science.