SLC7A11 enables a slow proton efflux from lysosomes and thus plays a vital role in maintaining the acidic environment inside these cellular organelles. This has been demonstrated by a new study published in Cell. Additionally, the authors have shown that SLC7A11 malfunction can lead to the aggregation of α-synuclein, a protein linked to the development of Parkinson’s disease.

Lysosomes are spherical vesicles within the cell that use digestive enzymes to break down large molecules, allowing essential components to be recycled and waste products to be removed from the cell. To function properly, lysosomes need to maintain an acidic pH inside. This is achieved by continuously pumping hydrogen ions into the lysosome, but some protons also need to be transported out to maintain balance. While TMEM175 channels are known to mediate a fast proton efflux, it was suspected that also a second, slower pathway existed that had not yet been revealed.

In the new study, researchers conducted extensive experiments using various knockout and knock-in cell lines, including fibroblasts from a Parkinson’s patient,-and a mouse model. They found that SLC7A11 transports the amino acids cystine and glutamate across the lysosomal membrane, and in doing so, indirectly carries protons out of the lysosome. If SLC7A11 is absent or inhibited, the lysosome becomes overly acidic. As a result, degradation processes are impaired, waste materials accumulate, and a specific form of cell death known as ferroptosis can be triggered.