biostudies-literatureCarosi JMUniversity of South AustraliaNational Health and Medical Research CouncilAustralian GovernmentThe Hospital Research Foundation GroupAustralian Research Council863-882https://www.ebi.ac.uk/biostudies/studies/S-EPMC11062367biostudies-literatureUnknown20(4)Retromer prevents the destruction of numerous receptors by recycling them from endosomes to the trans-Golgi network or plasma membrane. This enables retromer to fine-tune the activity of many signaling pathways in parallel. However, the mechanism(s) by which retromer function adapts to environmental fluctuations such as nutrient withdrawal and how this affects the fate of its cargoes remains incompletely understood. Here, we reveal that macroautophagy/autophagy inhibition by MTORC1 controls the abundance of retromer+ endosomes under nutrient-replete conditions. Autophagy activation by chemical inhibition of MTOR or nutrient withdrawal does not affect retromer assembly or its interaction with the RAB7 GAP protein TBC1D5, but rather targets these endosomes for bulk destructAutophagyAutophagy captures the retromer-TBC1D5 complex to inhibit receptor recycling.PMC11062367GNT11030062022-CF-EMCR-00720077391124490DP10100665Dang LVPCarosi JMSandow JJHein LKSargeant TJDenton DHattersley KKumar SfalseAutophagy captures the retromer-TBC1D5 complex to inhibit receptor recycling.Retromer prevents the destruction of numerous receptors by recycling them from endosomes to the trans-Golgi network or plasma membrane. This enables retromer to fine-tune the activity of many signaling pathways in parallel. However, the mechanism(s) by which retromer function adapts to environmental fluctuations such as nutrient withdrawal and how this affects the fate of its cargoes remains incompletely understood. Here, we reveal that macroautophagy/autophagy inhibition by MTORC1 controls the abundance of retromer+ endosomes under nutrient-replete conditions. Autophagy activation by chemical inhibition of MTOR or nutrient withdrawal does not affect retromer assembly or its interaction with the RAB7 GAP protein TBC1D5, but rather targets these endosomes for bulk destruct2024-01-01T00:00:00Z2024 Apr2026-06-03T05:27:56.543Z2025-04-04T02:57:35.081ZS-EPMC110623673793819610.1080/15548627.2023.2281126