How the SLC26A11 transporter enables recycling within brain and kidney cells

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by Inka Burow, Hannover Medical School

edited by Gaby Clark, reviewed by Robert Egan

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This molecular illustration shows the dual function: to ensure the smooth breakdown of proteins, the SLC26A11 protein acts as a transporter to remove sulphate waste and as a channel to expel the resulting chloride from the lysosome into the cell interior. Credit: Institut für Neurophysiologie, MHH

Our cells have their own internal "garbage collection" system that gathers up everything that is defective, worn out or foreign. Acting as a sort of "cellular stomach," the so-called lysosomes are responsible for this recycling process. However, the breakdown products must also be transported out of the organelles again; otherwise, there is a risk of neurological disorders, some of which can be severe. A research consortium led by the MHH has now discovered how this works, using sulfate in brain and kidney cells as an example.

Tidying up is essential in our everyday lives—and this also applies to human cells. They have their own waste collection system, which tracks down old cell components, foreign bodies such as bacteria, and waste products within the cell and encloses them in a sort of garbage bag. But nature is not wasteful, so cellular waste is not simply disposed of but broken down into its building blocks and recycled.

The task of these "recycling centers" is carried out by structures known as lysosomes. Among other things, they break down proteins, producing sulfate—a chemical compound of sulfur and oxygen—as a byproduct. However, the sulfate must also be removed from the lysosomes. If it accumulates unchecked, it impairs the work of the enzymes involved. Such disruptions can lead to a group of disorders known as lysosomal storage diseases. These include Sanfilippo syndrome, a fatal neurological disorder.

Despite its importance, the molecular machinery underpinning these mechanisms has remained largely unknown until now. A research team led by Prof. Dr. Jan-Philipp Machtens, director of the Institute of Neurophysiology at Hanover Medical School (MHH), in collaboration with the Jülich Research Centre and the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden, has now elucidated this pathway.

The researchers discovered that a specific enzyme in the lysosomal membrane is responsible for exporting excess sulfate from the lysosomes. The study has been published in the journal Nature Communications.

Lysosomes function as the 'stomach of the cell'

Lysosomes are large, acidic organelles found inside the cell. An organelle is a specialized, compartmentalized area within a cell that performs a specific function—much like our own organs. Lysosomes serve as the final destination for proteins that have reached the end of their lifespan.

They are sometimes referred to as the "stomach of the cell" and, like the stomach, have an acidic environment inside them. Just like the stomach, they digest whatever they enclose—material from outside the cell or from within it, such as proteins, carbohydrates, fatty acids and nucleic acids. These are broken down by enzymes, and the resulting components are transported through the lysosomal membrane into the cell interior, where they are then recycled.

"We were able to demonstrate that a membrane protein called SLC26A11, acting as the responsible transporter, regulates the sulfate concentration," Machtens says. The general presence of SLC26A11—particularly in kidney and brain cells—was already known. However, its exact location and function had previously been unclear. "In our study, we have now elucidated the function of SLC26A11 in lysosomes," explains the neurophysiologist.

The enzyme's dual function is crucial

In their studies, the researchers found that SLC26A11 has a dual function. First, as a transporter, it actively exports the sulfate produced during protein degradation out of the lysosomes—always together with a positively charged hydrogen atom and in exchange for a negatively charged chlorine atom, also known as a chloride ion. This transport coupling provides the energy required for efficient sulfate export from the acidic lysosome.

However, this would in turn lead to an accumulation of chloride there. SLC26A11 therefore has a second function as a chloride channel, which channels the accumulating chloride ions out again. "The dual function of SLC26A11 as a sulfate transporter and chloride channel is crucial in ensuring that lysosomes fulfill their role in protein degradation and that cells can efficiently dispose of this protein waste," emphasizes the neurophysiologist.

These findings could pave the way for new therapeutic approaches that target not only lysosomal storage disorders but also other neurological conditions associated with impaired chloride regulation in the lysosomes.

Publication details

Benedikt T. Kuhn et al, SLC26A11 is an atypical solute carrier with dual transport-channel function mediating lysosomal sulfate transport, Nature Communications (2026). DOI: 10.1038/s41467-026-75749-4

Journal information: Nature Communications

Key medical concepts

Lysosomal Storage Diseases

Clinical categories

Neurology Provided by Hannover Medical School Who's behind this story?

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