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线粒体动力学与精神障碍:缺失的环节。

Mitochondrial dynamics and psychiatric disorders: The missing link.

机构信息

Laboratory of Biochemistry, Department of Biological Applications and Technology, University of Ioannina, Greece; Biomedical Research Institute, Foundation for Research and Technology-Hellas, Ioannina, Greece.

Laboratory of Biochemistry, Department of Biological Applications and Technology, University of Ioannina, Greece; Biomedical Research Institute, Foundation for Research and Technology-Hellas, Ioannina, Greece; Institute of Biosciences, University of Ioannina, Greece.

出版信息

Neurosci Biobehav Rev. 2024 Oct;165:105837. doi: 10.1016/j.neubiorev.2024.105837. Epub 2024 Jul 30.

DOI:10.1016/j.neubiorev.2024.105837
PMID:39089419
Abstract

Elucidating the molecular mechanisms of psychopathology is crucial for optimized diagnosis and treatment. Accumulating data have underlined how mitochondrial bioenergetics affect major psychiatric disorders. However, how mitochondrial dynamics, a term addressing mitochondria quality control, including mitochondrial fission, fusion, biogenesis and mitophagy, is implicated in psychopathologies remains elusive. In this review, we summarize the existing literature on mitochondrial dynamics perturbations in psychiatric disorders/neuropsychiatric phenotypes. We include preclinical/clinical literature on mitochondrial dynamics recalibrations in anxiety, depression, post-traumatic stress disorder (PTSD), bipolar disorder and schizophrenia. We discuss alterations in mitochondrial network, morphology and shape, molecular markers of the mitochondrial dynamics machinery and mitochondrial DNA copy number (mtDNAcn) in animal models and human cohorts in brain and peripheral material. By looking for common altered mitochondrial dynamics patterns across diagnoses/phenotypes, we highlight mitophagy and biogenesis as regulators of anxiety and depression pathophysiology, respectively, as well as the fusion mediator dynamin-like 120 kDa protein (Opa1) as a molecular hub contributing to psychopathology. Finally, we comment on limitations and future directions in this novel neuropsychiatry field.

摘要

阐明精神病理学的分子机制对于优化诊断和治疗至关重要。越来越多的数据强调了线粒体生物能学如何影响主要的精神疾病。然而,线粒体动力学(一个涉及线粒体质量控制的术语,包括线粒体分裂、融合、生物发生和线粒体自噬)如何与精神病理学有关仍然难以捉摸。在这篇综述中,我们总结了精神障碍/神经精神表型中线粒体动力学紊乱的现有文献。我们包括了关于焦虑、抑郁、创伤后应激障碍(PTSD)、双相情感障碍和精神分裂症中线粒体动力学重新校准的临床前/临床文献。我们讨论了动物模型和人脑及外周组织中线粒体网络、形态和形状、线粒体动力学机制的分子标记物以及线粒体 DNA 拷贝数(mtDNAcn)的改变。通过寻找 across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across

阐明精神病理学的分子机制对于优化诊断和治疗至关重要。越来越多的数据强调了线粒体生物能学如何影响主要的精神疾病。然而,线粒体动力学(一个涉及线粒体质量控制的术语,包括线粒体分裂、融合、生物发生和线粒体自噬)如何与精神病理学有关仍然难以捉摸。在这篇综述中,我们总结了精神障碍/神经精神表型中线粒体动力学紊乱的现有文献。我们包括了关于焦虑、抑郁、创伤后应激障碍(PTSD)、双相情感障碍和精神分裂症中线粒体动力学重新校准的临床前/临床文献。我们讨论了动物模型和人脑及外周组织中线粒体网络、形态和形状、线粒体动力学机制的分子标记物以及线粒体 DNA 拷贝数(mtDNAcn)的改变。通过寻找 across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across across

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