Cargando…
Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential
Ischemic stroke (IS) accounts for more than 80% of the total stroke, which represents the leading cause of mortality and disability worldwide. Cerebral ischemia/reperfusion injury (CI/RI) is a cascade of pathophysiological events following the restoration of blood flow and reoxygenation, which not o...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244524/ https://www.ncbi.nlm.nih.gov/pubmed/37293623 http://dx.doi.org/10.3389/fncel.2023.1191629 |
_version_ | 1785054656578191360 |
---|---|
author | She, Ruining Liu, Danhong Liao, Jun Wang, Guozuo Ge, Jinwen Mei, Zhigang |
author_facet | She, Ruining Liu, Danhong Liao, Jun Wang, Guozuo Ge, Jinwen Mei, Zhigang |
author_sort | She, Ruining |
collection | PubMed |
description | Ischemic stroke (IS) accounts for more than 80% of the total stroke, which represents the leading cause of mortality and disability worldwide. Cerebral ischemia/reperfusion injury (CI/RI) is a cascade of pathophysiological events following the restoration of blood flow and reoxygenation, which not only directly damages brain tissue, but also enhances a series of pathological signaling cascades, contributing to inflammation, further aggravate the damage of brain tissue. Paradoxically, there are still no effective methods to prevent CI/RI, since the detailed underlying mechanisms remain vague. Mitochondrial dysfunctions, which are characterized by mitochondrial oxidative stress, Ca(2+) overload, iron dyshomeostasis, mitochondrial DNA (mtDNA) defects and mitochondrial quality control (MQC) disruption, are closely relevant to the pathological process of CI/RI. There is increasing evidence that mitochondrial dysfunctions play vital roles in the regulation of programmed cell deaths (PCDs) such as ferroptosis and PANoptosis, a newly proposed conception of cell deaths characterized by a unique form of innate immune inflammatory cell death that regulated by multifaceted PANoptosome complexes. In the present review, we highlight the mechanisms underlying mitochondrial dysfunctions and how this key event contributes to inflammatory response as well as cell death modes during CI/RI. Neuroprotective agents targeting mitochondrial dysfunctions may serve as a promising treatment strategy to alleviate serious secondary brain injuries. A comprehensive insight into mitochondrial dysfunctions-mediated PCDs can help provide more effective strategies to guide therapies of CI/RI in IS. |
format | Online Article Text |
id | pubmed-10244524 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102445242023-06-08 Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential She, Ruining Liu, Danhong Liao, Jun Wang, Guozuo Ge, Jinwen Mei, Zhigang Front Cell Neurosci Neuroscience Ischemic stroke (IS) accounts for more than 80% of the total stroke, which represents the leading cause of mortality and disability worldwide. Cerebral ischemia/reperfusion injury (CI/RI) is a cascade of pathophysiological events following the restoration of blood flow and reoxygenation, which not only directly damages brain tissue, but also enhances a series of pathological signaling cascades, contributing to inflammation, further aggravate the damage of brain tissue. Paradoxically, there are still no effective methods to prevent CI/RI, since the detailed underlying mechanisms remain vague. Mitochondrial dysfunctions, which are characterized by mitochondrial oxidative stress, Ca(2+) overload, iron dyshomeostasis, mitochondrial DNA (mtDNA) defects and mitochondrial quality control (MQC) disruption, are closely relevant to the pathological process of CI/RI. There is increasing evidence that mitochondrial dysfunctions play vital roles in the regulation of programmed cell deaths (PCDs) such as ferroptosis and PANoptosis, a newly proposed conception of cell deaths characterized by a unique form of innate immune inflammatory cell death that regulated by multifaceted PANoptosome complexes. In the present review, we highlight the mechanisms underlying mitochondrial dysfunctions and how this key event contributes to inflammatory response as well as cell death modes during CI/RI. Neuroprotective agents targeting mitochondrial dysfunctions may serve as a promising treatment strategy to alleviate serious secondary brain injuries. A comprehensive insight into mitochondrial dysfunctions-mediated PCDs can help provide more effective strategies to guide therapies of CI/RI in IS. Frontiers Media S.A. 2023-05-24 /pmc/articles/PMC10244524/ /pubmed/37293623 http://dx.doi.org/10.3389/fncel.2023.1191629 Text en Copyright © 2023 She, Liu, Liao, Wang, Ge and Mei. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience She, Ruining Liu, Danhong Liao, Jun Wang, Guozuo Ge, Jinwen Mei, Zhigang Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential |
title | Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential |
title_full | Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential |
title_fullStr | Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential |
title_full_unstemmed | Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential |
title_short | Mitochondrial dysfunctions induce PANoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential |
title_sort | mitochondrial dysfunctions induce panoptosis and ferroptosis in cerebral ischemia/reperfusion injury: from pathology to therapeutic potential |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10244524/ https://www.ncbi.nlm.nih.gov/pubmed/37293623 http://dx.doi.org/10.3389/fncel.2023.1191629 |
work_keys_str_mv | AT sheruining mitochondrialdysfunctionsinducepanoptosisandferroptosisincerebralischemiareperfusioninjuryfrompathologytotherapeuticpotential AT liudanhong mitochondrialdysfunctionsinducepanoptosisandferroptosisincerebralischemiareperfusioninjuryfrompathologytotherapeuticpotential AT liaojun mitochondrialdysfunctionsinducepanoptosisandferroptosisincerebralischemiareperfusioninjuryfrompathologytotherapeuticpotential AT wangguozuo mitochondrialdysfunctionsinducepanoptosisandferroptosisincerebralischemiareperfusioninjuryfrompathologytotherapeuticpotential AT gejinwen mitochondrialdysfunctionsinducepanoptosisandferroptosisincerebralischemiareperfusioninjuryfrompathologytotherapeuticpotential AT meizhigang mitochondrialdysfunctionsinducepanoptosisandferroptosisincerebralischemiareperfusioninjuryfrompathologytotherapeuticpotential |