Oliver's mTOR Atlas Evidence Platform
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Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule

Kelly G, Kataura T, Panek J, Ma G, Salmonowicz H, Davis A, Kendall H, Brookes C, von Zglinicki T, Miwa S, Carroll B, Reynisson J · 2024 · Developmental cell · Atlas ID KEL2024

What this study shows

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.

Abstract

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Selective degradation of damaged mitochondria by autophagy (mitophagy) is proposed to play an important role in cellular homeostasis. However, the molecular mechanisms and the requirement of mitochondrial quality control by mitophagy for cellular physiology are poorly understood. Here, we demonstrated that primary human cells maintain highly active basal mitophagy initiated by mitochondrial superoxide signaling. Mitophagy was found to be mediated by PINK1/Parkin-dependent pathway involving p62 as a selective autophagy receptor (SAR).

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At a glance

Evidence type M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Primary human cells; senescent and naturally aged cells) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type5 - Mechanistic / In Vitro
Model systemPrimary human cells; senescent and naturally aged cells
JournalDevelopmental cell
Year2024
Peer reviewedYes
Record last updated2026-09-23
SourceDOI 10.1016/j.devcel.2024.04.020 · PMID 38897197

Cite this paper

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Kelly, G., Kataura, T., Panek, J., Ma, G., Salmonowicz, H., Davis, A., Kendall, H., Brookes, C., von Zglinicki, T., Miwa, S., Carroll, B., Reynisson, J., & Korolchuk, V. I. (2024). Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule. Developmental cell. https://doi.org/10.1016/j.devcel.2024.04.020

@article{KEL2024,
  author       = {Kelly, G. and Kataura, T. and Panek, J. and Ma, G. and Salmonowicz, H. and Davis, A. and Kendall, H. and Brookes, C. and von Zglinicki, T. and Miwa, S. and Carroll, B. and Reynisson, J. and Korolchuk, V. I.},
  title        = {{Suppressed basal mitophagy drives cellular aging phenotypes that can be reversed by a p62-targeting small molecule}},
  journal      = {Developmental cell},
  year         = {2024},
  doi          = {10.1016/j.devcel.2024.04.020},
  note         = {PMID: 38897197},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper. 

Barton, O. (2026). Oliver's mTOR Atlas (record KEL2024) [Data set]. https://mtor-atlas.org/study/KEL2024/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_KEL2024,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record KEL2024},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/KEL2024/},
  doi          = {10.5281/zenodo.22059963}
}