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Updated: Jul 18, 2026
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Published on: April 17, 2026
Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death
Seong-Woon Yu1, Shaida A Andrabi, Hongmin Wang
1Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Summary
Poly(ADP-ribose) (PAR) polymer acts as a cell death signal, triggering apoptosis-inducing factor (AIF) release from mitochondria. This discovery clarifies the mechanism of PARP-1-dependent cell death.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis-inducing factor (AIF) is a mitochondrial protein involved in programmed cell death.
- Poly(ADP-ribose) polymerase-1 (PARP-1) activation is known to trigger AIF release, but the precise mechanism remains unclear.
Purpose of the Study:
- To elucidate the signaling pathway linking PARP-1 activation to AIF release.
- To identify the specific molecule responsible for inducing AIF release and subsequent cell death.
Main Methods:
- Investigated the role of poly(ADP-ribose) (PAR) polymer in AIF release.
- Utilized PAR glycohydrolase to degrade PAR polymer and assess its effect on AIF release.
- Examined the sensitivity of cells with reduced AIF levels to PARP-1 activation and PAR polymer.
Main Results:
- Identified PAR polymer as a critical cell death signal that directly induces AIF release from mitochondria.
- Demonstrated that PAR polymer mediates the translocation of AIF to the nucleus.
- Showed that PAR glycohydrolase inhibits PARP-1-dependent AIF release by degrading PAR polymer.
- Found that reduced AIF levels confer resistance to PARP-1-dependent cell death and PAR polymer toxicity.
Conclusions:
- PAR polymer functions as an AIF-releasing factor, playing a crucial role in PARP-1-mediated cell death.
- This study reveals a novel mechanism in programmed cell death pathways involving PAR polymer and AIF.
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