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Mitochondrial levels determine variability in cell death by modulating apoptotic gene expression

Author

Listed:
  • Silvia Márquez-Jurado

    (Campus de Cantoblanco)

  • Juan Díaz-Colunga

    (Campus de Cantoblanco)

  • Ricardo Pires Neves

    (Center of Innovation in Biotechnology)

  • Antonio Martinez-Lorente

    (Department of Pathology of Torrevieja and Vinalopó Hospitals
    Universidad de Alicante)

  • Fernando Almazán

    (Campus de Cantoblanco)

  • Raúl Guantes

    (Universidad Autónoma de Madrid, Campus de Cantoblanco)

  • Francisco J. Iborra

    (Campus de Cantoblanco
    Campus Burjassot/Paterna Parc Cientific)

Abstract

Fractional killing is the main cause of tumour resistance to chemotherapy. This phenomenon is observed even in genetically identical cancer cells in homogeneous microenvironments. To understand this variable resistance, here we investigate the individual responses to TRAIL in a clonal population of HeLa cells using live-cell microscopy and computational modelling. We show that the cellular mitochondrial content determines the apoptotic fate and modulates the time to death, cells with higher mitochondrial content are more prone to die. We find that all apoptotic protein levels are modulated by the mitochondrial content. Modelling the apoptotic network, we demonstrate that these correlations, and especially the differential control of anti- and pro-apoptotic protein pairs, confer mitochondria a powerful discriminatory capacity of apoptotic fate. We find a similar correlation between the mitochondria and apoptotic proteins in colon cancer biopsies. Our results reveal a different role of mitochondria in apoptosis as the global regulator of apoptotic protein expression.

Suggested Citation

  • Silvia Márquez-Jurado & Juan Díaz-Colunga & Ricardo Pires Neves & Antonio Martinez-Lorente & Fernando Almazán & Raúl Guantes & Francisco J. Iborra, 2018. "Mitochondrial levels determine variability in cell death by modulating apoptotic gene expression," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02787-4
    DOI: 10.1038/s41467-017-02787-4
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    Cited by:

    1. Dirke Imig & Nadine Pollak & Frank Allgöwer & Markus Rehm, 2020. "Sample-based modeling reveals bidirectional interplay between cell cycle progression and extrinsic apoptosis," PLOS Computational Biology, Public Library of Science, vol. 16(6), pages 1-17, June.

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