Component
Lysosome-associated AMPK activation
Lysosome-associated AMPK activation. Species, exposure and limitations are retained in each linked claim.
2 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
How nutrients reach it in more than one step
Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
What acts on it
Knockout of PEN2, or re-introduction of a PEN2 mutant that does not bind ATP6AP1, blunted AMPK activation.
Experimental context and source evidence
- availability_state
- machinery_impairment Imported condition classification; unverified.
- evidence_span
- {"source_cache": "artifacts/metformin-research/35197629.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "587594a8bbbf0a2baa7066264c0c46b26ded6231287176608885e736bee36983", "start_char": 0, "end_char": 1549, "text_sha256": "587594a8bbbf0a2baa7066264c0c46b26ded6231287176608885e736bee36983"}
- experimental_model
- Photoactive metformin probe, binding studies, knockouts in mice and C. elegans
- exposure
- Clinically relevant low metformin concentrations; PEN2 knockout and ATP6AP1-binding mutants
- limitations
- A direct binding partner at low dose with a micromolar dissociation constant. Lifespan and fat-content endpoints are model endpoints, not clinical outcomes.
- nutrient_topic
- Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
- organism
- Human cells, mouse and C. elegans
- plain_language
- Without that protein the switch is not thrown.
- primary_references
- [metformin-p35197629] Low-dose metformin targets the lysosomal AMPK pathway through PEN2. (2022). https://pubmed.ncbi.nlm.nih.gov/35197629/ DOI: 10.1038/s41586-022-04431-8
- tissue_or_cell_type
- Lysosome, liver and intestine
- trigger_kind
- machinery_impairment Imported condition classification; unverified.
Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 671–682
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Photoactive metformin probe, binding studies, knockouts in mice and C. elegans · source_derived_draft · unverified_draft
### metformin-pen2-null-ampk Knockout of PEN2, or re-introduction of a PEN2 mutant that does not bind ATP6AP1, blunted AMPK activation. Condition category: machinery_impairment nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: Without that protein the switch is not thrown. organism: Human cells, mouse and C. elegans tissue_or_cell_type: Lysosome, liver and intestine experimental_model: Photoactive metformin probe, binding studies, knockouts in mice and C. elegans limitations: A direct binding partner at low dose with a micromolar dissociation constant. Lifespan and fat-content endpoints are model endpoints, not clinical outcomes. exposure: Clinically relevant low metformin concentrations; PEN2 knockout and ATP6AP1-binding mutants evidence_span: {"source_cache": "artifacts/metformin-research/35197629.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "587594a8bbbf0a2baa7066264c0c46b26ded6231287176608885e736bee36983", "start_char": 0, "end_char": 1549, "text_sha256": "587594a8bbbf0a2baa7066264c0c46b26ded6231287176608885e736bee36983"} [metformin-p35197629] Low-dose metformin targets the lysosomal AMPK pathway through PEN2. (2022). https://pubmed.ncbi.nlm.nih.gov/35197629/ DOI: 10.1038/s41586-022-04431-8
Complete structured claim and evidence
Where it participates (unsigned role)
Clinically relevant concentrations of metformin inhibited the lysosomal proton pump v-ATPase, leading to AMPK activation without effects on cellular AMP levels.
Experimental context and source evidence
- evidence_span
- {"source_cache": "artifacts/metformin-research/35197629.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "587594a8bbbf0a2baa7066264c0c46b26ded6231287176608885e736bee36983", "start_char": 0, "end_char": 1549, "text_sha256": "587594a8bbbf0a2baa7066264c0c46b26ded6231287176608885e736bee36983"}
- experimental_model
- Photoactive metformin probe, binding studies, knockouts in mice and C. elegans
- exposure
- Clinically relevant low metformin concentrations; PEN2 knockout and ATP6AP1-binding mutants
- limitations
- A direct binding partner at low dose with a micromolar dissociation constant. Lifespan and fat-content endpoints are model endpoints, not clinical outcomes.
- nutrient_topic
- Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin
- organism
- Human cells, mouse and C. elegans
- plain_language
- The energy sensor is switched on at the lysosome rather than by a fall in cellular AMP.
- primary_references
- [metformin-p35197629] Low-dose metformin targets the lysosomal AMPK pathway through PEN2. (2022). https://pubmed.ncbi.nlm.nih.gov/35197629/ DOI: 10.1038/s41586-022-04431-8
- tissue_or_cell_type
- Lysosome, liver and intestine
Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 658–669
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Photoactive metformin probe, binding studies, knockouts in mice and C. elegans · source_derived_draft · unverified_draft
### metformin-vatpase-inhibition Clinically relevant concentrations of metformin inhibited the lysosomal proton pump v-ATPase, leading to AMPK activation without effects on cellular AMP levels. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: The energy sensor is switched on at the lysosome rather than by a fall in cellular AMP. organism: Human cells, mouse and C. elegans tissue_or_cell_type: Lysosome, liver and intestine experimental_model: Photoactive metformin probe, binding studies, knockouts in mice and C. elegans limitations: A direct binding partner at low dose with a micromolar dissociation constant. Lifespan and fat-content endpoints are model endpoints, not clinical outcomes. exposure: Clinically relevant low metformin concentrations; PEN2 knockout and ATP6AP1-binding mutants evidence_span: {"source_cache": "artifacts/metformin-research/35197629.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "587594a8bbbf0a2baa7066264c0c46b26ded6231287176608885e736bee36983", "start_char": 0, "end_char": 1549, "text_sha256": "587594a8bbbf0a2baa7066264c0c46b26ded6231287176608885e736bee36983"} [metformin-p35197629] Low-dose metformin targets the lysosomal AMPK pathway through PEN2. (2022). https://pubmed.ncbi.nlm.nih.gov/35197629/ DOI: 10.1038/s41586-022-04431-8
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.