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DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart
DJ-1 is a ubiquitously expressed protein that protects cells from stress through its conversion into an active protease. Recent work found that the active form of DJ-1 was induced in the ischemic heart as an endogenous mechanism to attenuate glycative stress—the non-enzymatic glycosylation of protei...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484662/ https://www.ncbi.nlm.nih.gov/pubmed/34593886 http://dx.doi.org/10.1038/s41598-021-98722-1 |
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author | Pantner, Yvanna Polavarapu, Rohini Chin, Lih-Shen Li, Lian Shimizu, Yuuki Calvert, John W. |
author_facet | Pantner, Yvanna Polavarapu, Rohini Chin, Lih-Shen Li, Lian Shimizu, Yuuki Calvert, John W. |
author_sort | Pantner, Yvanna |
collection | PubMed |
description | DJ-1 is a ubiquitously expressed protein that protects cells from stress through its conversion into an active protease. Recent work found that the active form of DJ-1 was induced in the ischemic heart as an endogenous mechanism to attenuate glycative stress—the non-enzymatic glycosylation of proteins. However, specific proteins protected from glycative stress by DJ-1 are not known. Given that mitochondrial electron transport proteins have a propensity for being targets of glycative stress, we investigated if DJ-1 regulates the glycation of Complex I and Complex III after myocardial ischemia–reperfusion (I/R) injury. Initial studies found that DJ-1 localized to the mitochondria and increased its interaction with Complex I and Complex III 3 days after the onset of myocardial I/R injury. Next, we investigated the role DJ-1 plays in modulating glycative stress in the mitochondria. Analysis revealed that compared to wild-type control mice, mitochondria from DJ-1 deficient (DJ-1 KO) hearts showed increased levels of glycative stress following I/R. Additionally, Complex I and Complex III glycation were found to be at higher levels in DJ-1 KO hearts. This corresponded with reduced complex activities, as well as reduced mitochondrial oxygen consumption ant ATP synthesis in the presence of pyruvate and malate. To further determine if DJ-1 influenced the glycation of the complexes, an adenoviral approach was used to over-express the active form of DJ-1(AAV9-DJ1ΔC). Under I/R conditions, the glycation of Complex I and Complex III were attenuated in hearts treated with AAV9-DJ1ΔC. This was accompanied by improvements in complex activities, oxygen consumption, and ATP production. Together, this data suggests that cardiac DJ-1 maintains Complex I and Complex III efficiency and mitochondrial function during the recovery from I/R injury. In elucidating a specific mechanism for DJ-1’s role in the post-ischemic heart, these data break new ground for potential therapeutic strategies using DJ-1 as a target. |
format | Online Article Text |
id | pubmed-8484662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84846622021-10-04 DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart Pantner, Yvanna Polavarapu, Rohini Chin, Lih-Shen Li, Lian Shimizu, Yuuki Calvert, John W. Sci Rep Article DJ-1 is a ubiquitously expressed protein that protects cells from stress through its conversion into an active protease. Recent work found that the active form of DJ-1 was induced in the ischemic heart as an endogenous mechanism to attenuate glycative stress—the non-enzymatic glycosylation of proteins. However, specific proteins protected from glycative stress by DJ-1 are not known. Given that mitochondrial electron transport proteins have a propensity for being targets of glycative stress, we investigated if DJ-1 regulates the glycation of Complex I and Complex III after myocardial ischemia–reperfusion (I/R) injury. Initial studies found that DJ-1 localized to the mitochondria and increased its interaction with Complex I and Complex III 3 days after the onset of myocardial I/R injury. Next, we investigated the role DJ-1 plays in modulating glycative stress in the mitochondria. Analysis revealed that compared to wild-type control mice, mitochondria from DJ-1 deficient (DJ-1 KO) hearts showed increased levels of glycative stress following I/R. Additionally, Complex I and Complex III glycation were found to be at higher levels in DJ-1 KO hearts. This corresponded with reduced complex activities, as well as reduced mitochondrial oxygen consumption ant ATP synthesis in the presence of pyruvate and malate. To further determine if DJ-1 influenced the glycation of the complexes, an adenoviral approach was used to over-express the active form of DJ-1(AAV9-DJ1ΔC). Under I/R conditions, the glycation of Complex I and Complex III were attenuated in hearts treated with AAV9-DJ1ΔC. This was accompanied by improvements in complex activities, oxygen consumption, and ATP production. Together, this data suggests that cardiac DJ-1 maintains Complex I and Complex III efficiency and mitochondrial function during the recovery from I/R injury. In elucidating a specific mechanism for DJ-1’s role in the post-ischemic heart, these data break new ground for potential therapeutic strategies using DJ-1 as a target. Nature Publishing Group UK 2021-09-30 /pmc/articles/PMC8484662/ /pubmed/34593886 http://dx.doi.org/10.1038/s41598-021-98722-1 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Pantner, Yvanna Polavarapu, Rohini Chin, Lih-Shen Li, Lian Shimizu, Yuuki Calvert, John W. DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart |
title | DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart |
title_full | DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart |
title_fullStr | DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart |
title_full_unstemmed | DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart |
title_short | DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart |
title_sort | dj-1 attenuates the glycation of mitochondrial complex i and complex iii in the post-ischemic heart |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484662/ https://www.ncbi.nlm.nih.gov/pubmed/34593886 http://dx.doi.org/10.1038/s41598-021-98722-1 |
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