RT Journal Article SR Electronic T1 Lamp1 mediates lipid transport, but is dispensable for autophagy in Drosophila JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.03.432938 DO 10.1101/2021.03.03.432938 A1 Norin Chaudhry A1 Margaux Sica A1 Satya Surabhi A1 David Sanchez Hernandez A1 Ana Mesquita A1 Adem Selimovic A1 Ayesha Riaz A1 Hua Bai A1 Gustavo C. Macintosh A1 Andreas Jenny YR 2021 UL http://biorxiv.org/content/early/2021/03/03/2021.03.03.432938.abstract AB The endolysosomal system not only is an integral part of the cellular catabolic machinery that processes and recycles nutrients for synthesis of biomaterials, but also acts as signaling hub to sense and coordinate the energy state of cells with growth and differentiation. Lysosomal dysfunction adversely influences vesicular transport-dependent macromolecular degradation and thus causes serious problems for human health. In mammalian cells, loss of the lysosome associated membrane proteins LAMP1/2 strongly impacts autophagy and cholesterol trafficking. Here we show that the previously uncharacterized Drosophila Lamp1 is a bona fide homolog of vertebrate LAMP1/2. Surprisingly and in contrast to Lamp1/2 double mutant mice, Drosophila Lamp1 is not required for viability or autophagy, suggesting that autophagy defects in Lamp1/2 mutants may have indirect causes. However, Lamp1 deficiency results in an expansion of the acidic compartment in flies. Furthermore, we find that Lamp1 mutant larvae have defects in lipid metabolism as they show elevated levels of sterols and diacylglycerols (DAGs). Since DAGs are the main lipid species used for transport though the hemolymph (blood) in insects, our results indicate broader functions of Lamp1 in lipid transport. Our findings make Drosophila an ideal model to study the role of LAMP proteins in lipid assimilation without the confounding effects of their storage and without interfering with autophagic processes.Competing Interest StatementThe authors have declared no competing interest.aaamino acidALautolysosomeAPGautophagosomeAPGLautophagolysosomeAVautophagic vacuole (i.e. APG and APGL/AL)AViearly/initial autophagic vacuolesAVdlate/degradative autophagic vacuolesAtgautophagy-relatedCMAchaperone mediated autophagyDAGdiacylglyceroleMIendosomal microautophagyESCRTendosomal sorting complexes required for transportFBfat bodyHDLhigh density lipoproteinLAMPlysosome associated membrane proteinLDlipid dropletLDLlow density lipoproteinLpplipophorinLtpLipid transfer proteinLTRLysotrackerMAmacroautophagyMEFmouse embryonic fibroblastmTORCmechanistic target of rapamycin complexPVparasitophorous vacuoleSNAREsoluble N-ethylmaleimide sensitive factor attachment protein receptorSnapsynaptosomal-associated proteinststarvedTAGtriacylglycerolTEMtransmission electron microscopyTFEBtranscription factor EBTMtransmembrane domaintubtubulinUTRuntranslated region.