Whoa—Scientists Found a Part of Human Cells We Never Knew Existed

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Here’s what you’ll learn when you read this story:

Hemifusomes are fused vesicles, or sacs of fluid, that were previously unknown to exist inside cells.
They were discovered using cryo-electron tomography, which literally freezes them in time, and confirmed to be actual organelles and not just background noise.
Because hemifusomes collect and recycle junk proteins, they could mean more effective treatments for diseases caused and aggravated by protein plaque buildup, such as Alzheimer’s.

Back in high school biology, most of us learned about the innards of a cell, or its organelles, from ribosomes to mitochondria to the endoplasmic reticulum, and probably had to identify them on our midterms. Now, an unexpected discovery will probably soon rewrite those textbooks.

The hemifusome is the new organelle that high school students (much to their chagrin) will have to remember. Biophysicist Seham Ebrahim of the University of Virginia and her team of researchers were observing mammalian cells when they discovered hemifusomes, which previously eluded detection because they are even smaller than mitochondria and can easily blur or be mistaken for background noise. These nano-orbs, which look like they have, noses bear an uncanny resemblance to BB-8 or the profiles of certain Muppets. Pop culture references aside, their function of organizing, cleaning up, and recycling proteins could potentially unlock new treatments for genetic and neurodegenerative diseases.

Hemifusomes consist of two vesicles, which are membrane sacs filled with liquid and formed by hemifusion, meaning that the smaller of the two is fused to the larger one like a hemisphere, almost as if its other half is missing. This occurs when the outer layers of two membranes merge first while the inner membrane layers stay open until a thin connection between them forms a new vesicle. The attached vesicles are sometimes found on the outside of the organelle and sometimes on the inside, and though where exactly these vesicles originate is still unknown, hemifusomes are thought to facilitate the formation of new vesicles that transport materials throughout the cell. This is probably how they take out cellular trash.

Ebrahim used cryo-electron tomography, or cryo-ET, to observe and image hemifusomes. The cells, which were kept at cryogenic temperatures, were imaged in two dimensions using an electron microscope. Superfast cameras then took multiple photos of the frozen cells and their organelles. From these photos, single images were created using algorithms, upgrading the 2D images to 3D.

“Our observation of hemifusomes in four different cell lines originating from various species and tissues and frozen as close as possible to their native state suggests that they may be common components of the cell periphery in a wide range of cells and tissues,” she said in a study recently published in Nature Communications.

Something else the researchers wanted to explore was what kind of relationship hemifusomes had with endosomes, which are vesicles that transport extracellular material into the cell via the process of endocytosis. The cell’s plasma membrane will fold inward to surround matter, such as food molecules, in the surrounding fluid. These molecules are then taken in by the cell, whose plasma membrane pinches off to create an endosome that carries them into the cytoplasm. Endosomes can also form through the fusion of vesicles that already exist within the cell. Ebrahim traced the activity of endosomes and hemifusomes, but they did not appear to work together.

What makes hemifusomes so important is how they collect and recycle junk proteins. Many studies have shown that the buildup of protein plaque in the brain can cause and aggravate neurodegenerative diseases such as dementia and Alzheimer’s, and more understanding about how these organelles operate could lead to the development of treatments that work with them.

“Future research should focus on determining whether hemifusomes and compound hemifusomes are present in other cellular regions,” Ebrahim said, “and on elucidating the molecular mechanisms underlying their formation, stability, and function, as well as their broader implications for cellular physiology and pathology.”

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