Lipid Droplets are active translation depots that respond to infection

Lipid droplets (LDs) are increasingly recognized as dynamic organelles with roles extending beyond lipid storage. While the core LD proteome across cells reveals minimal overlap, several proteins with "housekeeping" functions such as ribosomal proteins and translation factors have largely been ignored as contaminants. Here, we provide biochemical and microscopy-based evidence of ribosome components and the ribosome to be present in association with the LD. By developing a modified method based on puromycylation, we demonstrate that active ribosomes are localised in close-proximity of LDs, demonstrating that LDs serve as sites of active protein translation. By using Mycobacterium tuberculosis (Mtb) infection as a model, we show that LD-associated translation is regulated under infection conditions. Although the specific mRNAs translated on LDs remain to be identified, these findings reveal LDs as critical platforms for protein synthesis and provide insights into how the LD proteome is established. This work highlights the multifaceted role of LDs in cellular homeostasis and host-pathogen interactions. IMPORTANTO_LIManuscripts submitted to Review Commons are peer reviewed in a journal-agnostic way. C_LIO_LIUpon transfer of the peer reviewed preprint to a journal, the referee reports wil be available in ful to the handling editor. C_LIO_LIThe identity of the referees wil NOT be communicated to the authors unless the reviewers choose to sign their report. C_LIO_LIThe identity of the referee wil be confidentia ly disclosed to any a filiate journals to which the manuscript is transferred. C_LI GUIDELINESO_LIFor reviewers: https://www.reviewcommons.org/reviewers C_LIO_LIFor authors: https://www.reviewcommons.org/authors C_LI CONTACTThe Review Commons o fice can be contacted directly at: office@reviewcommons.org