SLC7A11 is an unconventional H+ transporter in lysosomes
Macromolecular degradation in lysosomes require maintenance of an acidic pH of 4.5–5.0.
The researchers in this study discovered, SLC7A11, the protein target of the ferroptosis-inducing compound erastin, that acts as an unconventional proton exporter in lysosomes and mediates a slow lysosomal H+ leak through downward flux of cystine and glutamate, two H+ equivalents with uniquely large but opposite concentration gradients across lysosomal membranes.
SLC7A11 regulates proteolytic degradation, ferroptotic cell death, and Parkinson’s disease pathology and its deficiency or inhibition caused lysosomal over-acidification, reduced degradation, accumulation of storage materials, and ferroptosis, as well as facilitated α-synuclein aggregation in neurons.
