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March 28, 2026Cell Death and DiseaseOpen Access

DCTPP1 orchestrates dCTP pool dynamics and mtDNA stability in quiescent cells

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Authors

BFBelén FernándezGPGuiomar Pérez-MorenoBMBlanca Martínez-Arribas

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Overview

Analysis reveals DCTPP1's key role in maintaining dCTP balance and mtDNA stability in quiescent cells, suggesting therapeutic targets.

Key Points

  • This research aims to determine the role of DCTPP1 in managing dCTP pools and mtDNA stability in non-dividing cells.
  • Analyzed pyrimidine metabolism enzymes in non-dividing cells
  • Investigated DCTPP1 localization during cell quiescence
  • Examined effects of DCTPP1 depletion on dNTP balances
  • Utilized an in vitro model of MNGIE for therapeutic relevance
  • DCTPP1 localized primarily to mitochondria during quiescence
  • Depletion of DCTPP1 caused increased dCTP and dGTP pools and activated the thymidylate synthesis pathway
  • Thymidine overloading reduced dCTP and mtDNA levels; DCTPP1 knockdown reversed these effects
  • Downregulation of DCTPP1 increased mtDNA copy number, suggesting a compensatory mechanism in dCTP depletion disorders.

Cite This Study

Fernández et al. (2026) studied this question.

synapsesocial.com/papers/69c771348bbfbc51511e1103https://doi.org/10.1038/s41419-026-08632-1
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