Mitophagy
Selective autophagic degradation of damaged or dysfunctional mitochondria; regulated by the AMPK-mTOR-ULK1 axis and implicated in cardiac protection, neurodegeneration, and aging.
Recycling worn-out power plants. The process of clearing out damaged mitochondria (the cell's power plants). It's controlled by the AMPK-mTOR-ULK1 signaling chain and may help protect the heart and brain as we age.
ULK1-dependent and partly PINK1/Parkin-dependent; measured in vivo mostly with reporter mice, so quantitative claims are model-bound.
TL;DR. Mitophagy appears in 3 curated studies in Oliver's mTOR Atlas: 2 in animal models; 1 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 1 interaction in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| AMPK activates Mitophagy mechanism: functional-consequence · this link in full · on the map table | The cell's energy sensor can help clear out damaged mitochondria, partly by switching on an autophagy starter kinase. How much it matters depends on the cell and on the kind of stress. AMPK can promote the clearance of damaged mitochondria, in part by phosphorylating ULK1: cells whose ULK1 cannot be phosphorylated by AMPK show defective mitophagy under starvation. How much AMPK contributes depends on the cell type and on the kind of energy stress. AMPK can promote the clearance of damaged mitochondria, in part by phosphorylating ULK1: cells whose ULK1 cannot be phosphorylated by AMPK show defective mitophagy under starvation. How much AMPK contributes depends on the cell type and on the kind of energy stress. Holds under: Two studies of different kinds: EGA2010 (cells and C. elegans, AMPK-site mutant of ULK1) and ZHU2026 (mouse toxicology model, where LKB1/AMPK loss also went with mitochondrial DNA leakage and liver inflammation; that downstream link is shown only there). The upstream step is disputed: Park, Lee and Kim (Nat Commun 2023, PMID 37225695, outside this corpus) report that under energy stress AMPK restrains ULK1 activation; see AMPK-ULK1. plausible in people, not shown directly · emerging, few independent studies | A | EGA2010, ZHU2026 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| A | Animal model | 2 |
| M | Molecular — cells, biochemistry, structure | 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 | Forsythoside A Alleviates Hypertensive Nephropathy by Promoting Mitophagy and Inhibiting Ferroptosis via ASCL1-CCNB1/mTOR Pathway. CUI2026 Forsythoside A binds ASCL1 and blocks the downstream CCNB1/mTOR axis, promoting mitophagy and suppressing ferroptosis to protect against Ang II-induced hypertensive nephropathy in mice — without lowering blood pressure. |
| 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. |
Related entities
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