Preprint Highlight: A lysosomal lipid transport pathway that enables cell survival under choline limitation

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 .