Lysosome expansion by selective translation of lysosomal transcripts during phagocyte activation [article]

Victoria E.B. Hipolito, Jacqueline Diaz, Kristofferson Tandoc, Amra Saric, Ivan Toposiviric, Roberto Botelho
2018 bioRxiv   pre-print
The mechanisms that govern organelle properties to suit the needs of a cell remain poorly defined. Lysosomes degrade cargo from various routes including endocytosis, phagocytosis and autophagy. For phagocytes, lysosomes are a kingpin organelle since they are essential to kill pathogens and process antigens. During phagocyte activation, lysosomes undergo a striking reorganization, changing from dozens of globular structures to a tubular network, in a process that requires the
more » ... phosphatidylinositol-3-kinase-Akt-mTOR signalling pathway. Here, we show that lysosomes also undergo a rapid expansion in volume and holding capacity during phagocyte activation. Lysosome expansion was paralleled by the induction of lysosomal proteins but this was unexpectedly independent of TFEB and TFE3 transcription factors, known to scale up lysosome biogenesis. Instead, we demonstrate a hitherto unappreciated mechanism of organelle expansion via mTOR-dependent increase in translation of mRNAs encoding key lysosomal proteins including LAMP1 and V-ATPase subunits. Collectively, we identified a mechanism of rapid organelle expansion and remodelling driven by selective enhancement of protein synthesis.
doi:10.1101/260257 fatcat:ixsw7cz4lfhizpxr4syezl52eu