Autophagy as a cell fate determinant facing drugs and trophic-nutritional deprivation

• Autores: Paolo Luca Mattiolo
• Directores de la Tesis: Judit Ribas i Fortuny (dir. tes.), Jacint Boix Torras (dir. tes.)
• Lectura: En la Universitat de Lleida ( España ) en 2016
• Idioma: inglés
• Tribunal Calificador de la Tesis: Abelardo López Rivas (presid.), Carles Cantí Nicolás (secret.), Cristina Muñoz-Pinedo (voc.)
• Programa de doctorado: Programa Oficial de Doctorado en Salud
• Materias:
  • Química
    • Bioquímica
      • Farmacología molecular
  • Ciencias de la vida
    • Biología celular
      • Cultivo celular
  • Ciencias médicas
    • Farmacodinámica
      • Mecanismos de acción de los medicamentos
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • The 1st part of the thesis demonstrates that autophagy promotes cell death by an intrinsic apoptotic pathway at the early times of trophic-nutritional deprivation. In this paradigm, autophagy also promotes apoptosis induced by anticancer drugs. At longer times, autophagy displays its assumed protective role on starved cells. Time, being the only determinant of the dual role of autophagy on cell fate, is a novelty that impinges on tumor biology and therapy. The 2nd part of the thesis focuses on the compound 2-phenylethynesulfonamide (PES) with a promising lethal selectivity for cancer cells, already published. PES is an inhibitor of Heat Shock Protein 70 and autophagy, thus impairing cell proteostasis. The thesis reveals a positive feed-back between reactive oxygen species and p53 in the PES mode of action. Finally, PES uncovers an unexpected pro-survival function of BAX protein, precisely the promotion of mitochondrial fusion.