Scientists discover ‘hemifusome,’ a new cellular structure key to cell health

Scientists discover ‘hemifusome,’ a new cellular structure key to cell health

The discovery of a new cellular organelle, the “hemifusome,” is reshaping our understanding of how cells manage internal cargo and could offer new insights into devastating genetic disorders.

At a Glance

  • Scientists from the University of Virginia and the U.S. National Institutes of Health have identified a previously unknown cellular structure, a transient organelle which they have named the hemifusome.
  • The research team employed a powerful imaging method called in situ cryo-electron tomography to visualize this delicate structure within cells without the use of disruptive chemical fixatives.
  • This newly found organelle acts as a dynamic platform where transport vesicles partially merge, serving as a crucial loading dock for sorting and processing internal cellular cargo.
  • The finding introduces a previously unknown biological pathway for creating multivesicular bodies that operate independently of the well-established Endosomal Sorting Complexes Required for Transport (ESCRT) protein complex inside the cell.
  • By revealing a new component of cellular maintenance, this discovery offers a promising new avenue for researching genetic disorders caused by faulty internal transport systems.

Scientists from the University of Virginia School of Medicine and the U.S. National Institutes of Health have identified a previously unknown cellular structure. This discovery could reshape our understanding of cellular maintenance and disease. Named the “hemifusome,” this transient organelle appears to play a crucial role in how cells manage internal cargo. The research, detailed in a new study published in Nature Communications, utilized advanced imaging to capture this structure in action, revealing a new pathway for sorting and processing materials within the cell.

These cryo-electron tomography images provide the first direct look at the newly discovered hemifusome. Panel (a) shows an overview of several hemifusomes (HF, colored yellow and green) within the cellular environment, alongside other organelles, such as multivesicular bodies (MVB). The detailed close-ups in (b) and (c) reveal the structure’s key components: two partially merged vesicles connected by a stable bridge, the hemifusion diaphragm (HD), which is held in place by a dense particle (asterisk) identified as a proteolipid nanodroplet. (Tavakoli et al., 2025)

The discovery was made possible by a powerful imaging technique called in situ cryo-electron tomography (cryo-ET). This method involves flash-freezing living cells, preserving their internal components in a near-native state without the need for chemical fixatives that can alter delicate structures. By examining four different types of mammalian cells, the team observed that hemifusomes are formed when two distinct vesicles—small, membrane-bound sacs that transport substances—partially merge. A stable membrane bridge maintains this connection, known as a hemifusion diaphragm, which is consistently associated with a tiny, 42-nanometer structure that the team identified as a proteolipid nanodroplet (PND).

According to the researchers’ model, the hemifusome acts as a dynamic platform for creating new vesicles. “You can think of vesicles like little delivery trucks inside the cell,” said Seham Ebrahim, a researcher at UVA’s Department of Molecular Physiology and Biological Physics, in a university press release. “The hemifusome is like a loading dock where they connect and transfer cargo.” This process is fundamental to the formation of cellular sorting centers known as multivesicular bodies (MVBs). Notably, this new mechanism for creating MVBs operates independently of the well-studied Endosomal Sorting Complexes Required for Transport (ESCRT) protein complex, which was previously considered the primary machinery for this task, suggesting that cells have a previously unknown system for managing their internal logistics.

This 3D reconstruction displays a single hemifusome, enabling viewers to view its structure from all angles. A stable bridge, the hemifusion diaphragm, joins two separate vesicles; at the center of this connection, a dense particle (the proteolipid nanodroplet) is visible, acting as a lynchpin that holds the entire complex together within the cell membrane. (Tavakoli et al., 2025)

This fundamental discovery has significant implications for understanding and potentially treating a range of inherited disorders linked to faulty cellular transport, such as Hermansky-Pudlak syndrome. This rare genetic condition can cause albinism, lung disease, and bleeding problems, all stemming from defects in how cells handle internal cargo. By providing a new blueprint for these essential processes, the identification of the hemifusome offers a fresh avenue for research. “It’s exciting because finding something truly new inside cells is rare—and it gives us a whole new path to explore,” Ebrahim said.


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