p62/SQSTM1
A protein that both helps mTORC1 switch on at the lysosome and normally gets swept up and destroyed during cellular cleanup. Scientists often read a pile-up of it as 'cleanup is broken', but that shortcut fails: in one kidney cancer it piles up while cleanup is running perfectly well. A pile-up is a question, not an answer.
TL;DR. p62/SQSTM1 appears in 5 curated studies in Oliver's mTOR Atlas: 2 in animal models; 2 at the molecular level (cells, biochemistry, structure); 1 review. No study in people is recorded for it in the Atlas yet.
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| A | Animal model | 2 |
| M | Molecular — cells, biochemistry, structure | 2 |
| 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 | PIP4K2A Attenuates Cerebral Ischemia/Reperfusion Injury by Reducing the TRIB3-p62 Complex Burden and Modulating AKT/mTOR Signaling. MA2026 PIP4K2A overexpression attenuates cerebral ischemia/reperfusion injury by reducing TRIB3-p62 complex burden and modulating AKT/mTOR signaling to restore autophagic flux, identifying PIP4K2A-AKT/mTOR as a neuroprotective axis in stroke. |
| 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 | 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. |
| 2026 | R | Molecular switches of SQSTM1: the impact of post-translational modifications on autophagy and neurodegeneration ABR2026 Comprehensive review of how post-translational modifications (phosphorylation, ubiquitination, acetylation, S-acylation, S-nitrosylation) tune SQSTM1/p62's role as the autophagy cargo-receptor hub -- relevant to neurodegenerative disease (Alzheimer's, ALS, Huntington's) where SQSTM1 regulation goes awry. |
| 2024 | M | Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule KEL2024 Healthy primary human cells run a high level of basal mitophagy, started by mitochondrial superoxide and carried out through the PINK1/Parkin pathway with p62 as the selective receptor. That housekeeping shuts down on entry into senescence and in naturally aged cells. Blocking mitophagy in young proliferating cells was by itself enough to trigger the senescence program, and reactivation of mitophagy was necessary for the anti-senescence effect of rapamycin and of NAD precursors, which places part of rapamycin's action on cellular ageing downstream of mitochondrial quality control rather than beside it. A p62-targeting small molecule restored mitophagy and rescued markers of cellular ageing. |
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