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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Poly(ADP-ribose) signaling in cell death.
László Virág1, Agnieszka Robaszkiewicz, Jose Manuel Rodriguez-Vargas
1Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary; MTA DE Cell Biology and Signaling Research Group, Debrecen, Hungary.
Molecular Aspects of Medicine
|February 19, 2013
Summary
Poly(ADP-ribosyl)ation (PARylation) regulates cell death pathways, including necroptosis, apoptosis, and autophagy. Uncontrolled poly(ADP-ribose) polymerase (PARP) activation contributes to cell demise via energetics, AIF translocation, and kinase crosstalk.
Area of Science:
- Cellular Biology
- Biochemistry
- Molecular Biology
Background:
- Poly(ADP-ribosyl)ation (PARylation) is a dynamic protein modification crucial for cellular functions.
- Dysregulated PARylation, particularly via poly(ADP-ribose) polymerase (PARP) activation, is linked to various cell death modalities.
- While PARylation's role in cell death is recognized, its precise molecular mechanisms are still being elucidated.
Purpose of the Study:
- To review the intricate molecular mechanisms of PARP-mediated cell death pathways.
- To explore the involvement of PARylation in necroptosis, apoptosis, and autophagy.
- To discuss recent advancements in understanding PARylation's role in cell demise.
Main Methods:
- Literature review of existing research on PARylation and cell death.
- Analysis of molecular pathways involved in PARP activation and its consequences.
- Synthesis of findings on PARylation's role in necroptosis, apoptosis, and autophagy.
Main Results:
- PARylation contributes to necroptosis through energy depletion (NAD+ loss), apoptosis-inducing factor (AIF) translocation (parthanatos), and crosstalk with cell death signaling kinases.
- PARylation's role in extrinsic and intrinsic apoptosis is context-dependent and less dominant than in necroptosis.
- Emerging evidence highlights PARylation's significant involvement in regulating autophagy and autophagic cell death.
Conclusions:
- PARylation is a key regulator of diverse cell death pathways, with necroptosis being significantly influenced by PARP activity.
- Understanding the interplay between PARylation and cell death signaling is critical for deciphering cellular responses to stress.
- Further research into PARylation's multifaceted roles in apoptosis and autophagy will provide deeper insights into cell fate determination.
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