Modulation of mitochondrial permeability transition pores in reperfusion injury: Mechanisms and therapeutic approaches.

IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL
Giampaolo Morciano, Paolo Pinton
{"title":"Modulation of mitochondrial permeability transition pores in reperfusion injury: Mechanisms and therapeutic approaches.","authors":"Giampaolo Morciano, Paolo Pinton","doi":"10.1111/eci.14331","DOIUrl":null,"url":null,"abstract":"<p><p>Ischemia/reperfusion injury is attracting continuous interest in science for two reasons: because it affects several clinical conditions and because it has been identified, albeit in broad terms, the molecular entity becoming activated by the reperfusion damage paradoxes. Indeed, calcium, oxygen-dependent oxidative stress and pH would activate conformational changes in the mitochondrial cristae embedded F<sub>1</sub>/F<sub>O</sub> ATP synthase, allowing the formation of pores in the inner mitochondrial membrane thus increasing its permeability. This is a key determinant for mitochondrial stress, cell death and tissue dysfunction. Targeting each of these factors has never contributed to improved clinical outcome of the patients affected by reperfusion damage; now, the focus on the PTP opening could represent the closest target to solve this pathway made by extensive cell death when the tissues become revascularized. In this review, we summarized last knowledge about the structure, the modulation and the therapeutic targeting of the PTP, focusing on ATP synthase and cardiac ischemia/reperfusion.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Clinical Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/eci.14331","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0

Abstract

Ischemia/reperfusion injury is attracting continuous interest in science for two reasons: because it affects several clinical conditions and because it has been identified, albeit in broad terms, the molecular entity becoming activated by the reperfusion damage paradoxes. Indeed, calcium, oxygen-dependent oxidative stress and pH would activate conformational changes in the mitochondrial cristae embedded F1/FO ATP synthase, allowing the formation of pores in the inner mitochondrial membrane thus increasing its permeability. This is a key determinant for mitochondrial stress, cell death and tissue dysfunction. Targeting each of these factors has never contributed to improved clinical outcome of the patients affected by reperfusion damage; now, the focus on the PTP opening could represent the closest target to solve this pathway made by extensive cell death when the tissues become revascularized. In this review, we summarized last knowledge about the structure, the modulation and the therapeutic targeting of the PTP, focusing on ATP synthase and cardiac ischemia/reperfusion.

再灌注损伤中线粒体通透性转换孔的调节:机制与治疗方法。
缺血/再灌注损伤正引起科学界的持续关注,原因有二:一是它影响着多种临床症状;二是它已被确定为再灌注损伤悖论所激活的分子实体,尽管只是广义上的。事实上,钙、氧依赖性氧化应激和 pH 会激活线粒体嵴中嵌入的 F1/FO ATP 合酶的构象变化,使线粒体内膜形成孔隙,从而增加其通透性。这是决定线粒体压力、细胞死亡和组织功能障碍的关键因素。针对这些因素中的每一个进行治疗都无助于改善受再灌注损伤影响的患者的临床预后;现在,关注 PTP 开放可能是解决组织血管再通时造成大量细胞死亡这一途径的最接近目标。在这篇综述中,我们总结了有关 PTP 结构、调节和治疗靶点的最新知识,重点关注 ATP 合酶和心脏缺血/再灌注。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
9.50
自引率
3.60%
发文量
192
审稿时长
1 months
期刊介绍: EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信