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Mol. Cells 2013; 36(3): 258-266

Published online August 29, 2013

https://doi.org/10.1007/s10059-013-0172-0

© The Korean Society for Molecular and Cellular Biology

Induction of Mitochondrial Dysfunction by Poly(ADP-Ribose) Polymer: Implication for Neuronal Cell Death

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

Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea, 1College of Pharmacy, Ajou University, Suwon 443-749, Korea, 2College of Pharmacy, Hanyang University, Ansan 426-791, Korea, 3These authors contributed equally to this work.

Received: June 5, 2013; Revised: June 22, 2013; Accepted: July 1, 2013

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) mediates neu-ronal 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, sig-nals 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

Article

Research Article

Mol. Cells 2013; 36(3): 258-266

Published online September 30, 2013 https://doi.org/10.1007/s10059-013-0172-0

Copyright © The Korean Society for Molecular and Cellular Biology.

Induction of Mitochondrial Dysfunction by Poly(ADP-Ribose) Polymer: Implication for Neuronal Cell Death

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

Department of Brain Science, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea, 1College of Pharmacy, Ajou University, Suwon 443-749, Korea, 2College of Pharmacy, Hanyang University, Ansan 426-791, Korea, 3These authors contributed equally to this work.

Received: June 5, 2013; Revised: June 22, 2013; Accepted: July 1, 2013

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) mediates neu-ronal 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, sig-nals 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

Mol. Cells
Feb 28, 2023 Vol.46 No.2, pp. 69~129
COVER PICTURE
The bulk tissue is a heterogeneous mixture of various cell types, which is depicted as a skein of intertwined threads with diverse colors each of which represents a unique cell type. Single-cell omics analysis untangles efficiently the skein according to the color by providing information of molecules at individual cells and interpretation of such information based on different cell types. The molecules that can be profiled at the individual cell by single-cell omics analysis includes DNA (bottom middle), RNA (bottom right), and protein (bottom left). This special issue reviews single-cell technologies and computational methods that have been developed for the single-cell omics analysis and how they have been applied to improve our understanding of the underlying mechanisms of biological and pathological phenomena at the single-cell level.

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