Seham Ebrahim, PhD
In a groundbreaking study published in Nature Communications, researchers from the University of Virginia School of Medicine and the National Institutes of Health (NIH) have discovered a previously unknown cellular structure—the hemifusome—that could fundamentally reshape our understanding of how cells recycle their contents and sort and direct intracellular cargo.
The discovery 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). It represents a major collaborative breakthrough powered by UVA’s Molecular Electron Microscopy Core (MEMC), a state-of-the-art cryo-electron microscopy facility directed by Michael Purdy, PhD.
“This is the first time anyone has visualized this structure inside cells,” said Dr. Ebrahim. “The hemifusome is a brand-new organelle, and we believe it plays a central role in a newly discovered pathway for building multivesicular bodies—key recycling centers within our cells.”
Multivesicular bodies (MVBs) help cells sort and remove unwanted proteins. They’re critical for processes like immune function, communication between cells, and protection against neurological diseases. Until now, researchers believed that nearly all MVBs formed using a protein-based system called ESCRT. The hemifusome, however, appears to follow a completely different path—one that relies on lipid-based remodeling rather than protein scaffolding.
These vesicle-like structures appeared in a unique, partially fused membrane state and were consistently associated with tiny lipid-rich droplets known as proteolipid nanodroplets (PNDs). Surprisingly, nearly 1 in 10 vesicles observed near the cell membrane were hemifusomes—underscoring their likely biological significance.
“The use of cryo-electron tomography, a cutting-edge imaging technique that flash-freezes cells and captures nanometer-resolution, 3D snapshots of their internal architecture, was essential to this discovery,” said Kachar. “It allowed us to see cellular structures that were completely invisible with conventional microscopy.”
The implications of this discovery are far-reaching. By revealing a new way that cells sort and move materials internally, this work could help scientists better understand diseases where these processes goes wrong, including Alzheimer’s, viral infections, and certain cancers.
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- A cryo-electron tomography image showing two hemifusomes—newly discovered organelles that may represent a previously unrecognized pathway for cellular recycling.
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- Cryo-electron tomography (left) and corresponding schematic (right) highlight the distinctive structure of a hemifusome, where two vesicle membranes connect through a hemifusion diaphragm. This configuration reveals a novel membrane topology not previously visualized in cells.
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