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
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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。
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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.
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