{"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.
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.