Savran Ozgur Yildirim, Tuncer Meltem
Department of Physiology, Faculty of Medicine, Hacettepe University, Ankara 06100, Turkey.
Life (Basel). 2025 Aug 11;15(8):1273. doi: 10.3390/life15081273.
Migraine is a complex neurological disorder characterized by recurrent headaches and sensory disturbances. Emerging evidence highlights a critical role for mitochondrial dysfunction in migraine pathophysiology, including impairments in oxidative phosphorylation, disruptions in mitochondrial dynamics, and altered biogenesis. Experimental migraine models-ranging from nitroglycerin-induced attacks to inflammatory stimuli-consistently demonstrate mitochondrial swelling, cristae disruption, decreased ATP production, and increased oxidative stress. These findings are accompanied by the altered expression of key mitochondrial regulators such as PGC-1α, Drp1, and Mfn1. Recent studies have further identified distinct metabolic subtypes of mitochondria, including P5CS-containing subsets, which exhibit unique structural and functional profiles, including cristae loss and reduced ATP synthase expression. Notably, the mitochondrial alterations observed in migraine models show remarkable parallels to those described in P5CS-related mitochondrial subsets. These similarities suggest a potential mechanistic link between metabolic reprogramming within mitochondria and migraine pathogenesis. Understanding the contribution of these newly defined mitochondrial populations could offer novel insights into migraine biology and open new avenues for targeted therapeutic strategies.
偏头痛是一种复杂的神经系统疾病，其特征为反复发作的头痛和感觉障碍。新出现的证据凸显了线粒体功能障碍在偏头痛病理生理学中的关键作用，包括氧化磷酸化受损、线粒体动力学紊乱以及生物合成改变。从硝酸甘油诱发发作到炎症刺激的实验性偏头痛模型一致显示出线粒体肿胀、嵴破坏、ATP生成减少以及氧化应激增加。这些发现伴随着关键线粒体调节因子如PGC-1α、Drp1和Mfn1的表达改变。最近的研究进一步确定了线粒体的不同代谢亚型，包括含P5CS的亚群，其表现出独特的结构和功能特征，包括嵴丢失和ATP合酶表达降低。值得注意的是，在偏头痛模型中观察到的线粒体改变与P5CS相关线粒体亚群中描述的改变非常相似。这些相似性表明线粒体代谢重编程与偏头痛发病机制之间存在潜在的机制联系。了解这些新定义的线粒体群体的作用可能为偏头痛生物学提供新的见解，并为靶向治疗策略开辟新途径。
