Mitochondrial dynamics and aggresome formation in human rpe cells under oxidative stress

• Autores: Luis Bonet Ponce
• Directores de la Tesis: Francisco Javier Romero Gómez (dir. tes.), Francisco Javier Sancho Pelluz (dir. tes.)
• Lectura: En la Universidad Católica de Valencia San Vicente Mártir ( España ) en 2015
• Idioma: inglés
• Tribunal Calificador de la Tesis: Joaquín Jordán Bueso (presid.), José Manuel Fuentes Rodríguez (secret.), Debasish Sinha (voc.)
• Materias:
  • Ciencias médicas
    • Ciencias clínicas
      • Oftalmología
    • Patología
      • Neuropatología
    • Farmacología
• Enlaces
  • Tesis en acceso abierto en: TESEO
• Resumen

  • Age-related macular degeneration (AMD) is a brutal neurodegenerative disease that constitutes the main cause of blindness worldwide. AMD is triggered by the death of retinal pigment epithelial (RPE) cells. At a cellular level, it is well established that an imbalance of the redox status triggers RPE degeneration. It is, therefore crucial to study the cellular and molecular mechanisms underlying ROS-induced damage in RPE cells.

    Although mitochondrial damage and misfolded proteins accumulation have been proposed to play a crucial role in AMD, nothing is known about its regulation or dynamics. Hence, our goal is to study mitochondrial dynamics and mitophagy, as well as aggresome dynamics and aggrephagy in cell culture models of AMD, such as ethanol and rotenone addition in ARPE-19 cells.

    We herein demonstrated that under ethanol exposure, mitochondria undergo fission. Consequently, mitochondrial-derived ROS activates autophagy in order to degrade fragmented mitochondria and protect cells from mitochondrial ROS. In addtition, ethanol-derived ROS induces aggresome formation in ARPE-19 cells. Interestingly, although rotenone addition also induces ROS-mediated aggresome formation, we observed that aggresome accumulation is the result of an impairment of autophagy flux, as a consequence of mitochondrial ROS production. Our data suggest an excessive tubulin acetylation as a possible cause of the autophagy impairment.

    Thus, our data provide novel information on the cellular mechanisms in the basis of ROS-mediated damage in human RPE cells. A correct function and regulation of autophagy is crucial to maintain cellular viability in RPE cells under stress conditions.