Lysosomes maintain cellular homeostasis by clearing macromolecules and recycling their content to support the cell's needs. Lysosomal dysfunction is also a common feature in many human diseases. However, the mechanisms underlying the recycling of many essential metabolites remain unknown.

The authors use a creative CRISPR-Cas9 screen to identify proteins involved in choline export from lysosomes to the cytosol. They identified SPNS1, a lysosomal transmembrane protein essential for cell growth under choline-depleted conditions. Targeted lipidomics on isolated lysosomes and isotope tracing revealed that SPNS1 transports lysophosphatidylcholine from lysosomes into the cytosol, where it is re-esterified into phosphatidylcholine.

This work defines a new pathway for lysosomal phospholipid egress and provides a reliable new screening method for the identification of novel lysosomal pathways.

This preprint has been assigned the following badges: New Hypothesis, New Methods, Cross-Validation.

Read the preprint on bioRxiv (Scharenberg et al., 2022): https://doi.org/10.1101/2022.11.27.517422.