Methionine
Essential sulfur-containing amino acid. The cell reads its supply in two ways: indirectly through its metabolite S-adenosylmethionine (SAM), which binds SAMTOR (GU2017), and, according to a 2026 chemoproteomic study in human cells (SANG2026), directly as free methionine bound by PKM2. Restricting methionine improves metabolic health and lifespan in animal models, as summarised in the review KNO2026, which is why these sensors matter for ageing research.
An essential amino acid the cell can read directly. An essential amino acid that the body cannot make. The cell keeps track of how much it has, partly through a molecule made from it (SAM) and possibly also by sensing methionine itself.
Two methionine readouts now sit side by side: SAM-SAMTOR acting at GATOR1-KICSTOR, and free methionine-PKM2 acting at GATOR2 (SANG2026, human cells, single study). Their relative weight under dietary methionine restriction is untested.
TL;DR. Methionine appears in 4 curated studies in Oliver's mTOR Atlas: 3 at the molecular level (cells, biochemistry, structure); 1 review. 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 |
|---|---|---|---|
| Methionine binds PKM2 mechanism: binding · this link in full · on the map table | Methionine sticks to PKM2. This does not switch the enzyme off; it just stops PKM2 from holding the brake on GATOR2. A second methionine detector next to SAMTOR. Holds under: One study in cultured human cells (SANG2026): photoaffinity chemoproteomics plus biochemical validation. No affinity measurement in tissue, no animal or human test, and not yet replicated by another group. The direction (methionine binding relieves PKM2's restraint on GATOR2) is taken from the authors' abstract; the full text was not accessible when this link was written. Parallel to, not a replacement for, SAM sensing by SAMTOR (SAM-SAMTOR): the two sensors read different molecules and act on different complexes (PKM2 on GATOR2, SAMTOR on GATOR1-KICSTOR). How much each contributes when methionine is restricted in a whole animal is untested. plausible in people, not shown directly · emerging, few independent studies | M | SANG2026 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| M | Molecular — cells, biochemistry, structure | 3 |
| 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 | M | "Trojan" Methionine Probe Reveals PKM2 as a Methionine-Sensing Protein in the mTORC1 Pathway SANG2026 Identifies PKM2 as a direct methionine sensor for mTORC1. A photoaffinity methionine analogue plus chemoproteomics showed that PKM2 binds free methionine through a distinct recognition pocket — independently of its glycolytic enzyme activity — and transduces methionine availability to mTORC1 via the GATOR2 complex. Complements SAMTOR (GU2017), which reads the methionine metabolite SAM rather than methionine itself, and suggests a route to a pharmacological "methionine pseudostarvation" state. |
| 2026 | R | The hallmarks of protein and amino acid restriction in aging and longevity KNO2026 Defines the "hallmarks" of dietary protein restriction (PR) through the lens of aging: PR and restriction of specific essential amino acids — especially methionine, isoleucine and valine — improve metabolic health, healthspan and lifespan across organisms, with amino-acid composition (not just protein quantity) acting as a key determinant via nutrient-sensing pathways including mTORC1. |
| 2021 | M | mTORC1 stimulates cell growth through SAM synthesis and m6A mRNA-dependent control of protein synthesis VIL2021 SAMTOR (GU2017) showed the cell can sense S-adenosylmethionine and report it to mTORC1. This study runs the arrow the other way: mTORC1 controls how much SAM the cell makes. Downstream of mTORC1, c-MYC binds intron 1 of MAT2A and raises expression of the enzyme that produces SAM, the cell's main methyl donor; mTORC1 separately increases the protein level of WTAP, the regulatory subunit of the m6A RNA methyltransferase complex. Together these raise m6A methylation of mRNA, which primes the translation machinery for growth. Blocking MAT2A lowers SAM, m6A, protein synthesis rate and tumor growth. |
| 2017 | M | SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway GU2017 Extended nutrient sensing beyond amino acids to METABOLITES: SAMTOR reads S-adenosylmethionine (SAM), the cell's methyl-donor currency, linking methionine and one-carbon metabolism to mTORC1. Relevant to why methionine restriction affects aging. |
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