Cell senescence is associated with permanent withdrawal from the cell cycle in response to various stresses and ageing. Kang et al. screened human fibroblasts for factors that alleviate senescence and identified the major DNA damage repair kinase ATM as one of the hits. ATM interacted with the subunits of the lysosomal proton pump, and by phosphorylating them prevented the functional association of the subunits. This led to an increase in lysosomal pH and interfered with the removal of dysfunctional mitochondria by autophagy. As a consequence, cells accumulated defective mitochondria, which resulted in metabolic dysfunction and senescence. Inhibition of ATM reversed these negative effects and prevented senescence. Thus, ATM promotes cell senescence, suggesting that controlled inhibition of ATM could potentially counteract senescence and ageing.
References
Kang, H. T. et al. Chemical screening identifies ATM as a target for alleviating senescence. Nat. Chem. Biol. http://dx.doi.org/10.1038/nchembio.2342 (2017)
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Strzyz, P. A new role for ATM. Nat Rev Mol Cell Biol 18, 277 (2017). https://doi.org/10.1038/nrm.2017.39
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DOI: https://doi.org/10.1038/nrm.2017.39
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