Mitochondria: the hidden engines of traumatic brain injury-driven neurodegeneration.

IF 4.2 3区 医学 Q2 NEUROSCIENCES
Frontiers in Cellular Neuroscience Pub Date : 2025-05-09 eCollection Date: 2025-01-01 DOI:10.3389/fncel.2025.1570596
Olusola A Olatona, Sydney P Sterben, Sahan B S Kansakar, Aviva J Symes, Volha Liaudanskaya
{"title":"Mitochondria: the hidden engines of traumatic brain injury-driven neurodegeneration.","authors":"Olusola A Olatona, Sydney P Sterben, Sahan B S Kansakar, Aviva J Symes, Volha Liaudanskaya","doi":"10.3389/fncel.2025.1570596","DOIUrl":null,"url":null,"abstract":"<p><p>Mitochondria play a critical role in brain energy metabolism, cellular signaling, and homeostasis, making their dysfunction a key driver of secondary injury progression in traumatic brain injury (TBI). This review explores the relationship between mitochondrial bioenergetics, metabolism, oxidative stress, and neuroinflammation in the post-TBI brain. Mitochondrial dysfunction disrupts adenosine triphosphate (ATP) production, exacerbates calcium dysregulation, and generates reactive oxygen species, triggering a cascade of neuronal damage and neurodegenerative processes. Moreover, damaged mitochondria release damage-associated molecular patterns (DAMPs) such as mitochondrial DNA (mtDNA), Cytochrome C, and ATP, triggering inflammatory pathways that amplify tissue injury. We discuss the metabolic shifts that occur post-TBI, including the transition from oxidative phosphorylation to glycolysis and the consequences of metabolic inflexibility. Potential therapeutic interventions targeting mitochondrial dynamics, bioenergetic support, and inflammation modulation are explored, highlighting emerging strategies such as mitochondrial-targeted antioxidants, metabolic substrate supplementation, and pharmacological regulators of mitochondrial permeability transition pores. Understanding these mechanisms is crucial for developing novel therapeutic approaches to mitigate neurodegeneration and enhance recovery following brain trauma.</p>","PeriodicalId":12432,"journal":{"name":"Frontiers in Cellular Neuroscience","volume":"19 ","pages":"1570596"},"PeriodicalIF":4.2000,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12098645/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cellular Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fncel.2025.1570596","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

Mitochondria play a critical role in brain energy metabolism, cellular signaling, and homeostasis, making their dysfunction a key driver of secondary injury progression in traumatic brain injury (TBI). This review explores the relationship between mitochondrial bioenergetics, metabolism, oxidative stress, and neuroinflammation in the post-TBI brain. Mitochondrial dysfunction disrupts adenosine triphosphate (ATP) production, exacerbates calcium dysregulation, and generates reactive oxygen species, triggering a cascade of neuronal damage and neurodegenerative processes. Moreover, damaged mitochondria release damage-associated molecular patterns (DAMPs) such as mitochondrial DNA (mtDNA), Cytochrome C, and ATP, triggering inflammatory pathways that amplify tissue injury. We discuss the metabolic shifts that occur post-TBI, including the transition from oxidative phosphorylation to glycolysis and the consequences of metabolic inflexibility. Potential therapeutic interventions targeting mitochondrial dynamics, bioenergetic support, and inflammation modulation are explored, highlighting emerging strategies such as mitochondrial-targeted antioxidants, metabolic substrate supplementation, and pharmacological regulators of mitochondrial permeability transition pores. Understanding these mechanisms is crucial for developing novel therapeutic approaches to mitigate neurodegeneration and enhance recovery following brain trauma.

线粒体:外伤性脑损伤驱动的神经变性的隐藏引擎。
线粒体在脑能量代谢、细胞信号传导和体内平衡中起着关键作用,其功能障碍是创伤性脑损伤(TBI)继发性损伤进展的关键驱动因素。本文综述了脑外伤后线粒体生物能量学、代谢、氧化应激和神经炎症之间的关系。线粒体功能障碍破坏三磷酸腺苷(ATP)的产生,加剧钙的失调,并产生活性氧,引发神经元损伤和神经退行性过程的级联反应。此外,受损的线粒体释放损伤相关分子模式(DAMPs),如线粒体DNA (mtDNA)、细胞色素C和ATP,引发炎症途径,放大组织损伤。我们讨论了脑外伤后发生的代谢转变,包括从氧化磷酸化到糖酵解的转变以及代谢不灵活性的后果。针对线粒体动力学、生物能量支持和炎症调节的潜在治疗干预措施进行了探索,重点介绍了新兴策略,如线粒体靶向抗氧化剂、代谢底物补充和线粒体通透性过渡孔的药理学调节。了解这些机制对于开发新的治疗方法来减轻神经变性和增强脑外伤后的恢复至关重要。
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
7.90
自引率
3.80%
发文量
627
审稿时长
6-12 weeks
期刊介绍: Frontiers in Cellular Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the cellular mechanisms underlying cell function in the nervous system across all species. Specialty Chief Editors Egidio D‘Angelo at the University of Pavia and Christian Hansel at the University of Chicago are supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
×
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