Poly(ADP-ribose) signals to mitochondrial AIF: A key event in parthanatos

Wang, Yingfei; Dawson, Valina L.; Dawson, Ted M.

doi:10.1016/j.expneurol.2009.03.020

Cited by 338 publications

(299 citation statements)

References 91 publications

(175 reference statements)

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“…PARP-1 has been critically implicated in the necroptosis induced by TNF in L929 cells 31 and more recently in parthanatos. 15,32 Our data showed that PARP-1 activity increased with time during the course of TRAIL-induced necroptosis and concomitantly resulted in increased ATP depletion. Indeed, PJ-34, a pharmacological inhibitor of PARP-1, and RNA interference targeting PARP-1 inhibited TRAIL-induced ATP depletion leading to a switch from necroptosis to apoptosis at acidic pHe, thus further supporting an active role of PARP-1 in determining the mode of death receptor-induced cell death.…”

Section: Discussionmentioning

confidence: 68%

TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation

et al. 2012

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Although TRAIL (tumor necrosis factor (TNF)-related apoptosis inducing ligand) is a well-known apoptosis inducer, we have previously demonstrated that acidic extracellular pH (pHe) switches TRAIL-induced apoptosis to regulated necrosis (or necroptosis) in human HT29 colon and HepG2 liver cancer cells. Here, we investigated the role of RIPK1 (receptor interacting protein kinase 1), RIPK3 and PARP-1 (poly (ADP-ribose) polymerase-1) in TRAIL-induced necroptosis in vitro and in concanavalin A (Con A)-induced murine hepatitis. Pretreatment of HT29 or HepG2 with pharmacological inhibitors of RIPK1 or PARP-1 (Nec-1 or PJ-34, respectively), or transient transfection with siRNAs against RIPK1 or RIPK3, inhibited both TRAILinduced necroptosis and PARP-1-dependent intracellular ATP depletion demonstrating that RIPK1 and RIPK3 were involved upstream of PARP-1 activation and ATP depletion. In the mouse model of Con A-induced hepatitis, where death of mouse hepatocytes is dependent on TRAIL and NKT (Natural Killer T) cells, PARP-1 activity was positively correlated with liver injury and hepatitis was prevented both by Nec-1 or PJ-34. These data provide new insights into TRAIL-induced necroptosis with PARP-1 being active effector downstream of RIPK1/RIPK3 initiators and suggest that pharmacological inhibitors of RIPKs and PARP-1 could be new treatment options for immune-mediated hepatitis.

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Section: Discussionmentioning

confidence: 68%

TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation

et al. 2012

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“…23,24 Along similar lines, PS exposure is not a prerogative of apoptotic cell death, as it also constitutes an early feature of parthanatos and netosis (see below). 25,26 Third, a cell death-associated biochemical process can develop at a sublethal or transient level, which does not lead to the cell demise. Thus, while full-blown mitochondrial outer membrane permeabilization (MOMP) constitutes a point-ofno-return of intrinsic apoptosis (see below), 20 limited extents of MOMP (i.e., concerning a fraction of the mitochondrial pool) and the consequent (localized) activation of caspase-3 have been shown to participate in several cell death-unrelated programs such as the differentiation of megakaryocytes and granulocytes.…”

Section: Pros and Cons Of Morphological Versus Biochemical Classificamentioning

confidence: 99%

Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

et al. 2011

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proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.

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“…Poly(ADP-ribose) (PAR) polymerase (PARP) enzymes catalyze the conversion of NAD + to polymers of PAR [3]. Although its role in the DNA damage response has long been recognized, recent works indicate that PAR itself acts to directly induce cell death through stimulation of apoptosis-inducing factor (AIF) release [4,5].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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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.

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Poly(ADP-ribose) signals to mitochondrial AIF: A key event in parthanatos

Cited by 338 publications

References 91 publications

TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation

TRAIL induces necroptosis involving RIPK1/RIPK3-dependent PARP-1 activation

Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

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

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