Viktor I. Korolchuk
Showed that where lysosomes sit inside the cell tunes mTORC1 activity to nutrient supply. His Newcastle lab found that senescent cells can no longer switch mTORC1 off when nutrients or growth factors are withdrawn, and studies how autophagy and mitophagy decline with age
Professor of Cell Biology, Biosciences Institute, Newcastle University (since 2024) · Reader, Newcastle University (2017–2024) · Lecturer, Institute of Ageing and Health, Newcastle University (2011–2017) · postdoc, University of Cambridge (2003–2011, David Rubinsztein lab) · postdoc, University of Bristol (2000–2003) · PhD in Biochemistry, Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv (2000)
Korolchuk Lab, Biosciences Institute, Newcastle University (Newcastle upon Tyne, England, United Kingdom) ↗ Bluesky@korolchuklab.bsky.social ↗ ORCID0000-0002-4071-592X ↗
Portrait: Newcastle University
In 2011, working in David Rubinsztein's lab in Cambridge, Korolchuk showed that mTORC1 activity depends on a variable that had received little attention: where the lysosome physically sits in the cell. With nutrients available, lysosomes move out towards the cell periphery, close to the plasma-membrane signalling modules, and mTORC1 is active there. Starvation changes intracellular pH and pulls them into a cluster around the nucleus, mTORC1 output falls, and autophagy is released. The same positioning also sets how fast autophagosomes fuse with lysosomes — so one variable governs both the start and the finish of autophagic flux.
Since starting his own group at Newcastle in 2011, he has worked the other end of the same problem: what mTORC1 does in cells that have stopped dividing. His lab showed that in senescent human cells mTORC1 is constitutively active and deaf to the removal of serum or amino acids, and that the fault lies upstream — a depolarised plasma membrane, defective primary cilia, and an internal amino acid pool kept topped up by autophagy. Correct those inputs and the cells die, which makes persistent mTORC1 signalling a survival dependency of senescent cells rather than a side effect of senescence.
More recently the lab has tied rapamycin's effect on cellular ageing to mitochondrial housekeeping: healthy primary human cells run a high level of basal mitophagy that shuts down in senescence, and reactivating it turned out to be necessary for the anti-senescence effect of both rapamycin and NAD precursors. Alongside the research, Korolchuk is the human selector behind Autophagy and mTOR (bims-auttor), the weekly curated literature report on biomed.news that has been running since February 2019 — the same slice of the literature this Atlas curates.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2011 | M | Lysosomal positioning coordinates cellular nutrient responses KOR2011 First author: showed lysosomal positioning coordinates mTORC1 signalling with autophagic flux, adding a spatial axis to nutrient sensing. |
| 2017 | M | Persistent mTORC1 signaling in cell senescence results from defects in amino acid and growth factor sensing CAR2017 Senior author: explained why mTORC1 stays switched on in senescent cells, and that they depend on it to survive. |
| 2018 | A | Rapamycin improves healthspan but not inflammaging in nfkb1 mice COR2018 Co-author: in nfkb1 mice rapamycin improved healthspan and lowered senescence markers without extending lifespan or reducing inflammaging. |
| 2021 | M | G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling PRE2021 Co-author on the Cell study showing G3BP1/2 tether the TSC complex to lysosomes and thereby suppress mTORC1. |
| 2024 | M | Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule KEL2024 Senior author: reactivation of basal mitophagy is required for the anti-senescence effect of rapamycin and NAD precursors. |
Co-authors in the Atlas
People with a profile here who share at least one study with Viktor I. Korolchuk.
- David C. Rubinsztein Showed that rapamycin induces autophagy to clear the toxic protein of Huntington's disease, and that where lysosomes sit inside a cell helps set mTORC1 activity