ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy
Metadatos
Mostrar el registro completo del ítemAutor
Rodríguez-Vargas, José Manuel; Ruiz Magaña, María José; Ruiz Ruiz, Carmen; Majuelos-Melguizo, Jara; Peralta-Leal, Andreína; Rodríguez, M.I.; Muñoz-Gámez, José Antonio; Ruiz de Almodóvar, Mariano; Siles, E.; López-Rivas, Abelardo; Jäättela, M.; Oliver, Francisco JavierEditorial
NATURE-SHANGAI INSTITUTES FOR BIOLOGICAL SCIENCES
Materia
Starvation Autophagy DNA damage PARP-1 mTOR AMPK
Fecha
2012-07Referencia bibliográfica
J.M. Rodríguez-Vargas, M.J. Ruiz-Magaña, C. Ruiz-Ruiz, J. Majuelos-Melguizo, A. Peralta-Leal, M.I. Rodríguez, J.A. Muñoz-Gámez, M. Ruiz de Almodóvar, E. Siles, A. López-Rivas, M. Jäättela y F.J. Oliver. ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy. Cell Res. 2012 Jul;22(7):1181-98
Patrocinador
This work was supported by Ministerio de Ciencia e Innovación (SAF2006-01094 and SAF2009-13281-C02-01), Fundación La Caixa (BM06-219-0) and Junta de Andalucía (P07-CTS-0239) to FJO; RTICC (RD06/0020/0068) to ALR.Resumen
In response to nutrient stress, cells start an autophagy program that can lead to adaptation or death. The mechanisms
underlying the signaling from starvation to the initiation of autophagy are not fully understood. In the current
study we show that the absence or inactivation of PARP-1 strongly delays starvation-induced autophagy. We have
found that DNA damage is an early event of starvation-induced autophagy as measured by γ-H2AX accumulation
and comet assay, with PARP-1 knockout cells displaying a reduction in both parameters. During starvation, ROSinduced
DNA damage activates PARP-1, leading to ATP depletion (an early event after nutrient deprivation). The
absence of PARP-1 blunted AMPK activation and prevented the complete loss of mTOR activity, leading to a delay
in autophagy. PARP-1 depletion favors apoptosis in starved cells, suggesting a pro-survival role of autophagy and
PARP-1 activation after nutrient deprivation. In vivo results show that neonates of PARP-1 mutant mice subjected
to acute starvation, also display deficient liver autophagy, implying a physiological role for PARP-1 in starvation-induced
autophagy. Thus, the PARP signaling pathway is a key regulator of the initial steps of autophagy commitment
following starvation.