脑缺血/再灌注损伤中线粒体复合物 I 损伤的机制。一种假说。
Mechanism of mitochondrial complex I damage in brain ischemia/reperfusion injury. A hypothesis.
机构信息
Division of Neonatology, Department of Pediatrics, Columbia University, William Black Building, 650 W 168th St, New York, NY 10032, United States of America.
Division of Neonatology, Department of Pediatrics, Columbia University, William Black Building, 650 W 168th St, New York, NY 10032, United States of America.
出版信息
Mol Cell Neurosci. 2019 Oct;100:103408. doi: 10.1016/j.mcn.2019.103408. Epub 2019 Sep 5.
Abstract
The purpose of this review is to integrate available data on the effect of brain ischemia/reperfusion (I/R) on mitochondrial complex I. Complex I is a key component of the mitochondrial respiratory chain and it is the only enzyme responsible for regenerating NAD for the maintenance of energy metabolism. The vulnerability of brain complex I to I/R injury has been observed in multiple animal models, but the mechanisms of enzyme damage have not been studied. This review summarizes old and new data on the effect of cerebral I/R on mitochondrial complex I, focusing on a recently discovered mechanism of the enzyme impairment. We found that the loss of the natural cofactor flavin mononucleotide (FMN) by complex I takes place after brain I/R. Reduced FMN dissociates from the enzyme if complex I is maintained under conditions of reverse electron transfer when mitochondria oxidize succinate accumulated during ischemia. The potential role of this process in the development of mitochondrial I/R damage in the brain is discussed.
摘要
本次综述的目的是整合现有的关于脑缺血/再灌注（I/R）对线粒体复合物 I 影响的数据。复合物 I 是线粒体呼吸链的关键组成部分，也是唯一负责为维持能量代谢再生 NAD 的酶。在多种动物模型中均观察到脑复合物 I 对 I/R 损伤的易感性，但酶损伤的机制尚未得到研究。本综述总结了关于脑 I/R 对线粒体复合物 I 影响的旧有和新数据，重点介绍了该酶损伤的一个新发现的机制。我们发现，脑 I/R 后复合物 I 失去了天然辅因子黄素单核苷酸（FMN）。如果在线粒体氧化缺血期间积累的琥珀酸盐时，复合物 I 保持逆电子转移条件，那么减少的 FMN 会从酶中解离。讨论了该过程在脑线粒体 I/R 损伤发展中的潜在作用。
相似文献
1
Mechanism of mitochondrial complex I damage in brain ischemia/reperfusion injury. A hypothesis.脑缺血/再灌注损伤中线粒体复合物 I 损伤的机制。一种假说。
Mol Cell Neurosci. 2019 Oct;100:103408. doi: 10.1016/j.mcn.2019.103408. Epub 2019 Sep 5.
2
Redox-Dependent Loss of Flavin by Mitochondrial Complex I in Brain Ischemia/Reperfusion Injury.脑缺血/再灌注损伤中线粒体复合物 I 通过氧化还原依赖性丢失黄素。
Antioxid Redox Signal. 2019 Sep 20;31(9):608-622. doi: 10.1089/ars.2018.7693. Epub 2019 Jul 1.
3
Critical Role of Flavin and Glutathione in Complex I-Mediated Bioenergetic Failure in Brain Ischemia/Reperfusion Injury.黄素和谷胱甘肽在脑缺血/再灌注损伤中复合 I 介导线粒体生物能量衰竭中的关键作用。
Stroke. 2018 May;49(5):1223-1231. doi: 10.1161/STROKEAHA.117.019687. Epub 2018 Apr 11.
4
Reverse electron transfer results in a loss of flavin from mitochondrial complex I: Potential mechanism for brain ischemia reperfusion injury.逆向电子传递导致线粒体复合体I中黄素的丢失：脑缺血再灌注损伤的潜在机制。
J Cereb Blood Flow Metab. 2017 Dec;37(12):3649-3658. doi: 10.1177/0271678X17730242. Epub 2017 Sep 15.
5
Brain Ischemia/Reperfusion Injury and Mitochondrial Complex I Damage.脑缺血/再灌注损伤与线粒体复合物 I 损伤。
Biochemistry (Mosc). 2019 Nov;84(11):1411-1423. doi: 10.1134/S0006297919110154.
6
Redox-dependent loss of flavin by mitochondria complex I is different in brain and heart.线粒体复合体I导致的黄素氧化还原依赖性损失在脑和心脏中存在差异。
Redox Biol. 2022 May;51:102258. doi: 10.1016/j.redox.2022.102258. Epub 2022 Feb 6.
7
Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS.琥珀酸的缺血性积累通过线粒体活性氧控制再灌注损伤。
Nature. 2014 Nov 20;515(7527):431-435. doi: 10.1038/nature13909. Epub 2014 Nov 5.
8
Astragalus membranaceus-Carthamus tinctorius herb pair antagonizes parthanatos in cerebral ischemia/reperfusion injury via regulating PARP-1/TAX1BP1-mediated mitochondrial respiratory chain complex I.黄芪-红花药对通过调节PARP-1/TAX1BP1介导的线粒体呼吸链复合体I拮抗脑缺血/再灌注损伤中的细胞焦亡。
J Ethnopharmacol. 2025 Jan 31;340:119260. doi: 10.1016/j.jep.2024.119260. Epub 2024 Dec 18.
9
Reperfusion promotes mitochondrial dysfunction following focal cerebral ischemia in rats.再灌注促进大鼠局灶性脑缺血后线粒体功能障碍。
PLoS One. 2012;7(9):e46498. doi: 10.1371/journal.pone.0046498. Epub 2012 Sep 28.
10
[Effect of ethanol extract of Gastrodiae Rhizoma on mitochondrial dysfunction in cerebral ischemia-reperfusion injury].天麻乙醇提取物对脑缺血再灌注损伤中线粒体功能障碍的影响
Zhongguo Zhong Yao Za Zhi. 2022 Oct;47(20):5564-5573. doi: 10.19540/j.cnki.cjcmm.20220613.708.
引用本文的文献
1
Dynamic mechanisms and targeted interventions in cerebral ischemia-reperfusion injury: pathological cascade from ischemia to reperfusion and promising therapeutic strategies.脑缺血再灌注损伤的动态机制及靶向干预：从缺血到再灌注的病理级联反应及有前景的治疗策略
Front Neurosci. 2025 Aug 18;19:1649533. doi: 10.3389/fnins.2025.1649533. eCollection 2025.
2
Mitochondrial responses to constant and cyclic hypoxia depend on the oxidized fuel in a hypoxia-tolerant marine bivalve Crassostrea gigas.耐低氧海洋双壳贝类太平洋牡蛎对恒化和循环低氧的线粒体反应取决于氧化燃料。
Sci Rep. 2024 Apr 26;14(1):9658. doi: 10.1038/s41598-024-60261-w.
3
Uncovering Sex-Specific Epigenetic Regulatory Mechanism Involving H3k9me2 in Neural Inflammation, Damage, and Recovery in the Internal Carotid Artery Occlusion Mouse Model.揭示涉及 H3k9me2 的性别特异性表观遗传调控机制在大脑中动脉闭塞小鼠模型中的神经炎症、损伤和恢复。
Neuromolecular Med. 2024 Feb 26;26(1):3. doi: 10.1007/s12017-023-08768-9.
4
NL-1 Promotes PINK1-Parkin-Mediated Mitophagy Through MitoNEET Inhibition in Subarachnoid Hemorrhage.NL-1 通过抑制线粒体 NEET 蛋白促进蛛网膜下腔出血中的 PINK1-Parkin 介导的线粒体自噬。
Neurochem Res. 2024 Jun;49(6):1506-1516. doi: 10.1007/s11064-023-04024-5. Epub 2023 Oct 12.
5
Effect of mitochondrial circulation on mitochondrial age density distribution.线粒体循环对线粒体年龄密度分布的影响。
Int J Numer Method Biomed Eng. 2023 Dec;39(12):e3770. doi: 10.1002/cnm.3770. Epub 2023 Sep 9.
6
Effectiveness of Polyphenols on Perinatal Brain Damage: A Systematic Review of Preclinical Studies.多酚对围产期脑损伤的有效性：临床前研究的系统评价
Foods. 2023 Jun 6;12(12):2278. doi: 10.3390/foods12122278.
7
Ginsenoside compound K protects against cerebral ischemia/reperfusion injury via Mul1/Mfn2-mediated mitochondrial dynamics and bioenergy.人参皂苷Compound K通过Mul1/Mfn2介导的线粒体动力学和生物能量保护免受脑缺血/再灌注损伤。
J Ginseng Res. 2023 May;47(3):408-419. doi: 10.1016/j.jgr.2022.10.004. Epub 2022 Oct 20.
8
Current Evidence and Future Perspectives to Implement Continuous and End-Ischemic Use of Normothermic and Oxygenated Hypothermic Machine Perfusion in Clinical Practice.在临床实践中实施常温及氧合低温机器灌注持续和缺血末期使用的当前证据及未来展望。
J Clin Med. 2023 Apr 29;12(9):3207. doi: 10.3390/jcm12093207.
9
Reverse Electron Transport at Mitochondrial Complex I in Ischemic Stroke, Aging, and Age-Related Diseases.缺血性中风、衰老及年龄相关性疾病中线粒体复合体I的逆向电子传递
Antioxidants (Basel). 2023 Apr 6;12(4):895. doi: 10.3390/antiox12040895.
10
Monoterpenoid Epoxidiol Ameliorates the Pathological Phenotypes of the Rotenone-Induced Parkinson's Disease Model by Alleviating Mitochondrial Dysfunction.单萜环氧化醇通过减轻线粒体功能障碍改善鱼藤酮诱导的帕金森病模型的病理表型。
Int J Mol Sci. 2023 Mar 19;24(6):5842. doi: 10.3390/ijms24065842.
本文引用的文献
1
The dependence of brain mitochondria reactive oxygen species production on oxygen level is linear, except when inhibited by antimycin A.脑线粒体活性氧产生对氧水平的依赖性是线性的，除非被抗霉素 A 抑制。
J Neurochem. 2019 Mar;148(6):731-745. doi: 10.1111/jnc.14654. Epub 2019 Jan 24.
2
Locking loop movement in the ubiquinone pocket of complex I disengages the proton pumps.在复合物 I 的泛醌口袋中，锁环运动使质子泵解耦。
Nat Commun. 2018 Oct 29;9(1):4500. doi: 10.1038/s41467-018-06955-y.
3
Mitochondrial complex I in the post-ischemic heart: reperfusion-mediated oxidative injury and protein cysteine sulfonation.缺血后心脏中的线粒体复合物 I：再灌注介导的氧化损伤和蛋白质半胱氨酸磺酸化。
J Mol Cell Cardiol. 2018 Aug;121:190-204. doi: 10.1016/j.yjmcc.2018.07.244. Epub 2018 Jul 20.
4
Clinical validation of blood/brain glutamate grabbing in acute ischemic stroke.急性缺血性脑卒中血脑谷氨酸抓取的临床验证。
Ann Neurol. 2018 Aug;84(2):260-273. doi: 10.1002/ana.25286. Epub 2018 Aug 22.
5
Critical Role of Flavin and Glutathione in Complex I-Mediated Bioenergetic Failure in Brain Ischemia/Reperfusion Injury.黄素和谷胱甘肽在脑缺血/再灌注损伤中复合 I 介导线粒体生物能量衰竭中的关键作用。
Stroke. 2018 May;49(5):1223-1231. doi: 10.1161/STROKEAHA.117.019687. Epub 2018 Apr 11.
6
Krebs cycle metabolites and preferential succinate oxidation following neonatal hypoxic-ischemic brain injury in mice.小鼠新生缺氧缺血性脑损伤后克雷布斯循环代谢物和优先琥珀酸氧化。
Pediatr Res. 2018 Feb;83(2):491-497. doi: 10.1038/pr.2017.277. Epub 2017 Dec 6.
7
Reverse electron transfer results in a loss of flavin from mitochondrial complex I: Potential mechanism for brain ischemia reperfusion injury.逆向电子传递导致线粒体复合体I中黄素的丢失：脑缺血再灌注损伤的潜在机制。
J Cereb Blood Flow Metab. 2017 Dec;37(12):3649-3658. doi: 10.1177/0271678X17730242. Epub 2017 Sep 15.
8
Atomic structure of the entire mammalian mitochondrial complex I.完整哺乳动物线粒体复合物I的原子结构。
Nature. 2016 Oct 20;538(7625):406-410. doi: 10.1038/nature19794. Epub 2016 Sep 5.
9
Reversible FMN dissociation from Escherichia coli respiratory complex I.大肠杆菌呼吸链复合体I中黄素单核苷酸的可逆解离
Biochim Biophys Acta. 2016 Nov;1857(11):1777-1785. doi: 10.1016/j.bbabio.2016.08.008. Epub 2016 Aug 27.
10
Structure of mammalian respiratory complex I.哺乳动物呼吸链复合体I的结构。
Nature. 2016 Aug 18;536(7616):354-358. doi: 10.1038/nature19095. Epub 2016 Aug 10.
Zotero 插件