ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy

José Manuel Rodríguez-Vargas; María José Ruiz-Magaña; Carmen Ruiz-Ruiz; Jara Majuelos-Melguizo; Andreína Peralta-Leal; María Isabel Rodríguez; José Antonio Muñoz-Gámez; Mariano Ruiz de Almodóvar; Eva Siles; Abelardo López Rivas; Marja Jaattela; F Javier Oliver

doi:10.1038/cr.2012.70

ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy

José Manuel Rodríguez-Vargas, María José Ruiz-Magaña, Carmen Ruiz-Ruiz, Jara Majuelos-Melguizo, Andreína Peralta-Leal, María Isabel Rodríguez, José Antonio Muñoz-Gámez, Mariano Ruiz de Almodóvar, Eva Siles, Abelardo López Rivas, Marja Jaattela, F Javier Oliver

Morphogenesis and Differentiation Program

144 Citations (Scopus)

Abstract

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, ROS-induced 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.

Original language	English
Journal	Endocytobiosis and Cell Research
Volume	22
Issue number	7
Pages (from-to)	1181-98
Number of pages	18
ISSN	0256-1514
DOIs	https://doi.org/10.1038/cr.2012.70
Publication status	Published - Jul 2012

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Rodríguez-Vargas, J. M., Ruiz-Magaña, M. J., Ruiz-Ruiz, C., Majuelos-Melguizo, J., Peralta-Leal, A., Rodríguez, M. I., Muñoz-Gámez, J. A., de Almodóvar, M. R., Siles, E., Rivas, A. L., Jaattela, M., & Oliver, F. J. (2012). ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy. Endocytobiosis and Cell Research, 22(7), 1181-98. https://doi.org/10.1038/cr.2012.70

Rodríguez-Vargas, JM, Ruiz-Magaña, MJ, Ruiz-Ruiz, C, Majuelos-Melguizo, J, Peralta-Leal, A, Rodríguez, MI, Muñoz-Gámez, JA, de Almodóvar, MR, Siles, E, Rivas, AL, Jaattela, M & Oliver, FJ 2012, 'ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy', Endocytobiosis and Cell Research, vol. 22, no. 7, pp. 1181-98. https://doi.org/10.1038/cr.2012.70

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title = "ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy",

abstract = "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, ROS-induced 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.",

author = "Rodr{\'i}guez-Vargas, {Jos{\'e} Manuel} and Ruiz-Maga{\~n}a, {Mar{\'i}a Jos{\'e}} and Carmen Ruiz-Ruiz and Jara Majuelos-Melguizo and Andre{\'i}na Peralta-Leal and Rodr{\'i}guez, {Mar{\'i}a Isabel} and Mu{\~n}oz-G{\'a}mez, {Jos{\'e} Antonio} and {de Almod{\'o}var}, {Mariano Ruiz} and Eva Siles and Rivas, {Abelardo L{\'o}pez} and Marja Jaattela and Oliver, {F Javier}",

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T1 - ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy

AU - Rodríguez-Vargas, José Manuel

AU - Ruiz-Magaña, María José

AU - Ruiz-Ruiz, Carmen

AU - Majuelos-Melguizo, Jara

AU - Peralta-Leal, Andreína

AU - Rodríguez, María Isabel

AU - Muñoz-Gámez, José Antonio

AU - de Almodóvar, Mariano Ruiz

AU - Siles, Eva

AU - Rivas, Abelardo López

AU - Jaattela, Marja

AU - Oliver, F Javier

PY - 2012/7

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N2 - 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, ROS-induced 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.

AB - 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, ROS-induced 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.

U2 - 10.1038/cr.2012.70

DO - 10.1038/cr.2012.70

M3 - Journal article

C2 - 22525338

SN - 0256-1514

VL - 22

SP - 1181

EP - 1198

JO - Endocytobiosis and Cell Research

JF - Endocytobiosis and Cell Research

IS - 7

ER -

ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy

Abstract

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