Induction of mitochondrial dysfunction by poly(ADP-ribose) polymer: Implication for neuronal cell death

Seung Hoon Baek; Ok Nam Bae; Eun Kyoung Kim; Seong Woon Yu

doi:10.1007/s10059-013-0172-0

Induction of mitochondrial dysfunction by poly(ADP-ribose) polymer: Implication for neuronal cell death

Seung Hoon Baek, Ok Nam Bae, Eun Kyoung Kim, Seong Woon Yu

Department of Brain Sciences

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) mediates neuronal cell death in a variety of pathological conditions involving severe DNA damage. Poly(ADP-ribose) (PAR) polymer is a product synthesized by PARP-1. Previous studies suggest that PAR polymer heralds mitochondrial apoptosis-inducing factor (AIF) release and thereby, signals neuronal cell death. However, the details of the effects of PAR polymer on mitochondria remain to be elucidated. Here we report the effects of PAR polymer on mitochondria in cells in situ and isolated brain mitochondria in vitro. We found that PAR polymer causes depolarization of mitochondrial membrane potential and opening of the mitochondrial permeability transition pore early after injury. Furthermore, PAR polymer specifically induces AIF release, but not cytochrome c from isolated brain mitochondria. These data suggest PAR polymer as an endogenous mitochondrial toxin and will further our understanding of the PARP-1-dependent neuronal cell death paradigm.

Original language	English
Pages (from-to)	258-266
Number of pages	9
Journal	Molecules and Cells
Volume	36
Issue number	3
DOIs	https://doi.org/10.1007/s10059-013-0172-0
State	Published - Sep 2013

Bibliographical note

Funding Information:
This work was supported by the DGIST Convergence Science Center Program (13-BD-04) and MIREBrain program, and by the Korea Research Foundation Grant (KRF-2007-357-E00003).

Keywords

Apoptosis-inducing factor
Mitochondria
Neuronal cell death
Poly(ADP-ribose) polymer

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10.1007/s10059-013-0172-0

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title = "Induction of mitochondrial dysfunction by poly(ADP-ribose) polymer: Implication for neuronal cell death",

abstract = "Poly(ADP-ribose) polymerase-1 (PARP-1) mediates neuronal cell death in a variety of pathological conditions involving severe DNA damage. Poly(ADP-ribose) (PAR) polymer is a product synthesized by PARP-1. Previous studies suggest that PAR polymer heralds mitochondrial apoptosis-inducing factor (AIF) release and thereby, signals neuronal cell death. However, the details of the effects of PAR polymer on mitochondria remain to be elucidated. Here we report the effects of PAR polymer on mitochondria in cells in situ and isolated brain mitochondria in vitro. We found that PAR polymer causes depolarization of mitochondrial membrane potential and opening of the mitochondrial permeability transition pore early after injury. Furthermore, PAR polymer specifically induces AIF release, but not cytochrome c from isolated brain mitochondria. These data suggest PAR polymer as an endogenous mitochondrial toxin and will further our understanding of the PARP-1-dependent neuronal cell death paradigm.",

keywords = "Apoptosis-inducing factor, Mitochondria, Neuronal cell death, Poly(ADP-ribose) polymer",

author = "Baek, {Seung Hoon} and Bae, {Ok Nam} and Kim, {Eun Kyoung} and Yu, {Seong Woon}",

note = "Funding Information: This work was supported by the DGIST Convergence Science Center Program (13-BD-04) and MIREBrain program, and by the Korea Research Foundation Grant (KRF-2007-357-E00003).",

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AU - Baek, Seung Hoon

AU - Bae, Ok Nam

AU - Kim, Eun Kyoung

AU - Yu, Seong Woon

N1 - Funding Information: This work was supported by the DGIST Convergence Science Center Program (13-BD-04) and MIREBrain program, and by the Korea Research Foundation Grant (KRF-2007-357-E00003).

PY - 2013/9

Y1 - 2013/9

N2 - Poly(ADP-ribose) polymerase-1 (PARP-1) mediates neuronal cell death in a variety of pathological conditions involving severe DNA damage. Poly(ADP-ribose) (PAR) polymer is a product synthesized by PARP-1. Previous studies suggest that PAR polymer heralds mitochondrial apoptosis-inducing factor (AIF) release and thereby, signals neuronal cell death. However, the details of the effects of PAR polymer on mitochondria remain to be elucidated. Here we report the effects of PAR polymer on mitochondria in cells in situ and isolated brain mitochondria in vitro. We found that PAR polymer causes depolarization of mitochondrial membrane potential and opening of the mitochondrial permeability transition pore early after injury. Furthermore, PAR polymer specifically induces AIF release, but not cytochrome c from isolated brain mitochondria. These data suggest PAR polymer as an endogenous mitochondrial toxin and will further our understanding of the PARP-1-dependent neuronal cell death paradigm.

AB - Poly(ADP-ribose) polymerase-1 (PARP-1) mediates neuronal cell death in a variety of pathological conditions involving severe DNA damage. Poly(ADP-ribose) (PAR) polymer is a product synthesized by PARP-1. Previous studies suggest that PAR polymer heralds mitochondrial apoptosis-inducing factor (AIF) release and thereby, signals neuronal cell death. However, the details of the effects of PAR polymer on mitochondria remain to be elucidated. Here we report the effects of PAR polymer on mitochondria in cells in situ and isolated brain mitochondria in vitro. We found that PAR polymer causes depolarization of mitochondrial membrane potential and opening of the mitochondrial permeability transition pore early after injury. Furthermore, PAR polymer specifically induces AIF release, but not cytochrome c from isolated brain mitochondria. These data suggest PAR polymer as an endogenous mitochondrial toxin and will further our understanding of the PARP-1-dependent neuronal cell death paradigm.

KW - Apoptosis-inducing factor

KW - Mitochondria

KW - Neuronal cell death

KW - Poly(ADP-ribose) polymer

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SN - 1016-8478

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JO - Molecules and Cells

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Induction of mitochondrial dysfunction by poly(ADP-ribose) polymer: Implication for neuronal cell death

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Keywords

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