DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart

Abstract 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...

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Autores principales:	Yvanna Pantner, Rohini Polavarapu, Lih-Shen Chin, Lian Li, Yuuki Shimizu, John W. Calvert
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/edca3d41b4134b81ac974e626b3347aa
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spelling	oai:doaj.org-article:edca3d41b4134b81ac974e626b3347aa2021-12-02T17:37:40ZDJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart10.1038/s41598-021-98722-12045-2322https://doaj.org/article/edca3d41b4134b81ac974e626b3347aa2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98722-1https://doaj.org/toc/2045-2322Abstract 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.Yvanna PantnerRohini PolavarapuLih-Shen ChinLian LiYuuki ShimizuJohn W. CalvertNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yvanna Pantner Rohini Polavarapu Lih-Shen Chin Lian Li Yuuki Shimizu John W. Calvert DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart
description	Abstract 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	article
author	Yvanna Pantner Rohini Polavarapu Lih-Shen Chin Lian Li Yuuki Shimizu John W. Calvert
author_facet	Yvanna Pantner Rohini Polavarapu Lih-Shen Chin Lian Li Yuuki Shimizu John W. Calvert
author_sort	Yvanna Pantner
title	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_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_sort	dj-1 attenuates the glycation of mitochondrial complex i and complex iii in the post-ischemic heart
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/edca3d41b4134b81ac974e626b3347aa
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DJ-1 attenuates the glycation of mitochondrial complex I and complex III in the post-ischemic heart

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