Lamp1 mediates lipid transport, but is dispensable for autophagy in Drosophila

Chaudhry, Norin
Sica, Margaux
Surabhi, Satya
Hernandez, David Sanchez
Mesquita, Ana
Selimovic, Adem
Riaz, Ayesha
Lescat, Laury
Bai, Hua
Macintosh, Gustavo
Jenny, Andreas
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© 2022 Informa UK Limited
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Biochemistry, Biophysics and Molecular BiologyGenetics, Development and Cell Biology
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.
This is a manuscript of an article published as Chaudhry, Norin, Margaux Sica, Satya Surabhi, David Sanchez Hernandez, Ana Mesquita, Adem Selimovic, Ayesha Riaz et al. "Lamp1 mediates lipid transport, but is dispensable for autophagy in Drosophila." Autophagy (2022). doi: Posted with permission.