Autophagy
Cellular recycling process suppressed by mTORC1 and activated upon its inhibition; linked to longevity.
The cell eating its own worn-out parts.
Regulated at initiation (ULK1), at transcription (TFEB) and at fusion; most 'autophagy is required' claims rest on flux measurements that are hard to do in tissue.
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| A | Animal model | 9 |
| M | Molecular — cells, biochemistry, structure | 8 |
| R | Review — secondary literature, not a new result | 1 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2026 | A | Urolithin A activates mitophagy via the AMPK-mTOR axis and modulates the gut-ceramide axis to ameliorate cardiac remodeling in HFpEF SONH2026 Urolithin A ameliorates HFpEF cardiac remodeling in mice by activating AMPK and inhibiting mTOR to restore mitophagic flux, while simultaneously remodeling the gut microbiome-ceramide axis to reduce lipotoxic stress. |
| 2026 | A | Testosterone propionate maintains autophagic flux and mitochondrial integrity via regulation of the LC3B/p62/Beclin-1/mTOR axis in induced liver fibrosis. VER2026 Testosterone propionate protects against CCl4-induced liver fibrosis by maintaining mTOR-regulated autophagic flux via the LC3B/p62/Beclin-1 axis, preserving mitochondrial integrity; castration worsens fibrosis by impairing this pathway. |
| 2026 | A | Notoginsenoside R1 Alleviates Acetaminophen-Induced Liver Injury via MAPK/mTOR-Mediated Autophagy. LIS2026 Notoginsenoside R1 alleviates acetaminophen-induced acute liver injury by activating protective autophagy through MAPK/mTOR pathway modulation, reducing hepatocyte death and oxidative damage. |
| 2013 | A | Overexpression of Atg5 in mice activates autophagy and extends lifespan PYO2013 Mice engineered with extra copies of the autophagy gene Atg5 lived 17% longer and were leaner and more insulin-sensitive. |
| 2010 | A | Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster BJE2010 Feeding rapamycin extended fly lifespan through autophagy and reduced translation, and worked even in flies already on a lifespan-maximizing diet. |
| 2010 | A | Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease SPI2010 Connected the longevity drug to a specific age-related disease. Long-term rapamycin prevented memory deficits and lowered toxic amyloid-beta in an Alzheimer's mouse model - and the benefit tracked with INCREASED autophagy in neurons. Suggested that the same autophagy boost that may slow aging could also help clear disease-causing proteins. |
| 2010 | A | Molecular interplay between mTOR, amyloid-beta, and Tau: effects on cognitive impairments CAC2010 Revealed a vicious cycle: amyloid-beta RAISES mTOR activity, and high mTOR in turn blocks the autophagy needed to clear amyloid and tau - so the disease feeds itself. Rapamycin broke the loop in 3xTg-AD mice, rescuing memory and lowering BOTH amyloid and tau, with autophagy shown to be required for the effect. |
| 2004 | A | Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease RAV2004 Rapamycin-induced autophagy cleared toxic clumped proteins and improved symptoms in fly and mouse models of Huntington's disease. |
| 2003 | A | Autophagy genes are essential for dauer development and life-span extension in C. elegans MEL2003 Worms lacking the autophagy gene bec-1 lost the lifespan-extending benefit of reduced insulin-like signaling - autophagy is mechanistically required for longevity, not just correlated. |
| 2026 | M | Molecular and metabolic dysregulation of lung cancer in developing anti-tumor activity by gambogic acid mediated mTOR signaling: in vitro and computational study. BO2026 Gambogic acid exerts anti-tumor activity in lung cancer cells primarily by targeting and inhibiting mTOR signaling, supported by computational docking and in vitro experiments in cell lines; no in vivo or human data. |
| 2026 | M | FLCN loss is characterized by SQSTM1/p62 accumulation despite functional autophagy flux in Birt-Hogg-Dubé syndrome-associated kidney cancer ULL2026 In BHD patient-derived kidney cancer cells, FLCN loss causes constitutive nuclear TFEB localization and mTORC1 hyperactivation, but leaves bulk autophagy flux and LC3 lipidation unaffected; however, the autophagy receptor SQSTM1/p62 accumulates in enlarged puncta, a finding replicated in a Norwegian cohort of BHD patient kidney tumors, showing p62 accumulation is dissociable from bulk autophagic flux. |
| 2024 | M | mTORC1 activity oscillates throughout the cell cycle, promoting mitotic entry and differentially influencing autophagy induction JOS2024 mTORC1 activity oscillates across the cell cycle (lowest in mitosis/G1, highest in S/G2) via the TSC complex, independent of Akt/Mek-Erk; low mTORC1 in G1 sensitizes cells to autophagy induction from the same partial inhibition or nutrient drop -- direct evidence that the TIMING/pattern of mTORC1 activity, not just its average level, shapes autophagy outcome. |
| 2020 | R | mTOR at the nexus of nutrition, growth, ageing and disease LIU2020 The flagship modern review of the whole field, from Sabatini's own lab (Nature Reviews Molecular Cell Biology). Maps 25+ years of mTOR biology - how it senses nutrients, controls growth and autophagy, and goes wrong in cancer, neurodegeneration, metabolic disease and aging. The single best orientation document for the entire Atlas. |
| 2012 | M | MTORC1 functions as a transcriptional regulator of autophagy by preventing nuclear transport of TFEB MAR2012 Pinned down the direct mTORC1-TFEB link: mTORC1 (docked at the lysosome via Ragulator) phosphorylates TFEB on Ser211, which traps it in the cytosol via 14-3-3 proteins. Inhibit mTORC1 and TFEB rushes to the nucleus to switch on autophagy - explaining how mTORC1 controls recycling at the level of gene transcription. |
| 2011 | M | Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop LOF2011 ULK1 phosphorylates and inhibits AMPK in return, showing autophagy signaling is a bidirectional feedback loop, not a one-way switch. |
| 2011 | M | TFEB links autophagy to lysosomal biogenesis SET2011 Established TFEB as the single master switch that coordinates the WHOLE recycling program - it turns on both autophagosome and lysosome genes at once during starvation. This is the transcription factor that the mTORC1 pathway keeps switched off when nutrients are plentiful (mechanism pinned down by companion papers). |
| 2011 | M | AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 KIM2011 Revealed the tug-of-war over ULK1: the energy sensor AMPK phosphorylates ULK1 at activating sites to turn autophagy ON when energy is low, while mTORC1 phosphorylates a different site (Ser757) to keep it OFF and even blocks AMPK from reaching ULK1. Two opposing kinases wired to the same switch. |
| 2009 | M | Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy HOS2009 Showed the DIRECT brake mTORC1 uses on autophagy: when nutrients are plentiful, mTORC1 physically joins the ULK1-Atg13-FIP200 complex (the autophagy-starter kinase) and phosphorylates ULK1 to keep it off. Starvation or rapamycin releases this brake and autophagy begins. |