Summary: For years, scientists believed that permanent hearing loss was primarily caused by the failure of “ion channels” to send sound signals to the brain. However, a new study has uncovered a hidden culprit.
The proteins essential for hearing—TMC1 and TMC2—also act as “lipid scramblases” that maintain the integrity of cell membranes. When these proteins malfunction due to noise, genetics, or even common antibiotics, they flip fatty molecules to the wrong side of the membrane, triggering a “suicide signal” that kills the hair cells. Since these cells do not regenerate, this process leads to permanent deafness.
Key Facts
- The Dual Job: TMC1 and TMC2 aren’t just sound-to-signal converters; they are gatekeepers that shuffle phospholipids across the cell membrane.
- The Apoptotic Signal: When the phospholipid phosphatidylserine is flipped to the outer surface of the cell, it signals that the cell is dying (apoptosis). This “scrambling” is what actually kills hair cells.
- Antibotic Side Effects: Common antibiotics (aminoglycosides) were found to activate this lethal scramblase activity, explaining why they often cause permanent hearing loss.
- Cholesterol Connection: The study found that cholesterol levels in the cell membrane regulate this scrambling activity, suggesting that diet or cholesterol management might help protect hearing.
- Potential for Repair: Understanding this mechanism allows scientists to design new drugs (like hearing-safe antibiotics) that don’t trigger the “death flip.”
Source: Biophysical Society
Proteins long known to be essential for hearing have been hiding a talent: they also act as gatekeepers that shuffle fatty molecules across cell membranes.
When this newly discovered function goes haywire—due to genetic mutations, noise-induced damage, or certain medications—it may be what kills the delicate sensory cells in our ears, causing permanent hearing loss.
The research will be presented at the 70th Biophysical Society Annual Meeting in San Francisco from February 21–25, 2026.
Deep inside our ears, specialized cells called hair cells convert sound vibrations into electrical signals that travel to the brain. These cells get their name from tiny hair-like projections, called stereocilia, arranged in bundles that resemble a mohawk.
“When sound vibrations bend these hair-like structures, it opens channels that let ions flow into the cell, triggering a signal that carry sound to the brain,” explained Hubert Lee, a postdoctoral fellow in the lab of Angela Ballesteros at the National Institute on Deafness and Other Communication Disorders (NIDCD) at the National Institutes of Health.
“But when there’s a problem with these channel proteins, the hair cells die. And these cells don’t regenerate—so the hearing loss is permanent.”
The channel proteins in question, called TMC1 and TMC2, have been studied for years as the molecular machinery that converts sound into electrical signals. Mutations in TMC1 are a leading cause of genetic deafness. But the NIDCD team has now discovered these proteins have an entirely separate job.
“We found that TMC1 and TMC2 are not only ion channels important for hearing—they also regulate the cell membrane,” said Ballesteros. “And we think this membrane regulatory function, not the channel function, is what leads to hair cell death when things go wrong.”
The channels also act as “lipid scramblases”—molecular machines that move fatty molecules called phospholipids from one side of a cell membrane to the other. Normally, different types of phospholipids are kept on specific sides of the membrane. When one particular phospholipid, called phosphatidylserine, gets flipped to the outer surface of a cell, it’s often a signal that the cell is dying.
“Hair cells from mouse models carrying mutations in TMC1 that cause hearing loss exhibit this membrane dysregulation—phosphatidylserine gets externalized, and the membrane starts blebbing and falling apart,” Ballesteros said. “This is an apoptotic hallmark. It’s what’s killing the hair cells.”
The discovery also sheds light on why certain medications cause hearing loss as a side effect. Common antibiotics called aminoglycosides are known to damage hearing, and the researchers found these drugs activate the same membrane-disrupting scramblase activity in vivo.
“Scientists initially thought these drugs caused hearing loss by blocking the channel function of TMCs in vivo,” Lee said.
“But what we’re seeing now is that in the chaotic environment of the living hair cell, these drugs act as potent disruptors, triggering a collapse of membrane asymmetry. Yet, in the serene isolation of our reconstituted system, the protein remains indifferent to them, suggesting that other factors, such as lipid specificity or missing protein partners, are at play.”
The team also discovered that the scramblase activity depends on cholesterol levels in the cell membrane—a finding that could point toward future treatments based on diet or cholesterol management that could someday help protect our ears from ototoxic medications or genetic hearing loss.
“If we understand the mechanism by which these drugs activate the scramblase, we might be able to design new drugs that lack this effect,” said Yein Christina Park, graduate student at the NIH-JHU program and co-first author of this work. “We could potentially have antibiotics that don’t cause permanent hearing loss.”
Key Questions Answered:
A: Humans are born with a fixed number of sensory hair cells in the ear. Unlike skin or bone cells, these hair cells cannot regenerate. Once the “scramble” signal tells them to die, they are gone forever.
A: Yes. Some common antibiotics, called aminoglycosides, are “ototoxic.” This study shows they essentially “short-circuit” the proteins in your ear, causing the cell membranes to fall apart and the cells to commit suicide.
A: Cholesterol helps stabilize the cell membranes in your ear. The researchers found that the “death signal” depends on cholesterol levels, meaning that managing membrane health could be a future way to prevent hearing loss from noise or drugs.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this auditory neuroscience and hearing loss research news
Author: Leann Fox
Source: Biophysical Society
Contact: Leann Fox – Biophysical Society
Image: The image is credited to Neuroscience News
Original Research: The findings will be presented at the 70th Biophysical Society Annual Meeting
