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Title: Mitochondrial impairment triggers cytosolic oxidative stress and cell death following proteasome inhibition
Authors: Maharjan, Sunita
Oku, Masahide  kyouindb  KAKEN_id  orcid (unconfirmed)
Tsuda, Masashi
Hoseki, Jun  kyouindb  KAKEN_id
Sakai, Yasuyoshi  kyouindb  KAKEN_id
Author's alias: 奥, 公秀
寳関, 淳
阪井, 康能
Keywords: Cellular imaging
Issue Date: 31-Jul-2014
Publisher: Nature Publishing Group
Journal title: Scientific Reports
Volume: 4
Thesis number: 5896
Abstract: Dysfunctions of the mitochondria and the ubiquitin–proteasome system, as well as generation of reactive oxygen species (ROS), are linked to many aging-related neurodegenerative disorders. However, the order of these events remains unclear. Here, we show that the initial impairment occurs in mitochondria under proteasome inhibition. Fluorescent redox probe measurements revealed that proteasome inhibition led to mitochondrial oxidation followed by cytosolic oxidation, which could be prevented by a mitochondrial-targeted antioxidant or antioxidative enzyme. These observations demonstrated that proteasome dysfunction causes damage to mitochondria, leading them to increase their ROS production and resulting in cytosolic oxidation. Moreover, several antioxidants found in foods prevented intracellular oxidation and improved cell survival by maintaining mitochondrial membrane potential and reducing mitochondrial ROS generation. However, these antioxidant treatments did not decrease the accumulation of protein aggregates caused by inhibition of the proteasome. These results suggested that antioxidative protection of mitochondria maintains cellular integrity, providing novel insights into the mechanisms of cell death caused by proteasome dysfunction.
Description: タンパク質分解装置の活性低下が細胞死を引き起こす初期経路の同定と食品成分による回復. 京都大学プレスリリース. 2014-07-31.
Rights: This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material.
DOI(Published Version): 10.1038/srep05896
PubMed ID: 25077633
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