线粒体疾病是一组导致复杂神经退行性疾病的严重病理，在大多数情况下，没有治疗方法或治疗方法。这些细胞器是神经系统神经发生和稳态的关键调节因子。因此，线粒体损伤或功能障碍可能是神经发育或神经退行性疾病的原因或后果。随着神经发育障碍遗传知识的进步，编码线粒体蛋白的基因与神经系统症状（如神经病、脑肌病、共济失调、癫痫发作和发育迟缓等）之间的关联已被确定。了解线粒体功能障碍如何改变这些过程对于研究罕见疾病至关重要。三维 (3D) 细胞培养物可自组装形成由不同细胞类型组成的特殊结构，是模拟器官发生和神经发育障碍的一种可行方式。特别是，脑类器官正在彻底改变基于线粒体的神经系统疾病的研究，因为它们是器官特异性的并且是从患者细胞生成的模型，从而克服了传统动物和细胞模型的一些局限性。在这篇综述中，我们收集了在不同类型的已报道的大脑类器官中概括的神经结构和功能，重点关注那些作为线粒体疾病模型生成的类器官。除了脑类器官生成方面的进展之外，研究神经元结构和生理学的技术和方法也取得了进展，还对在线粒体损伤和神经发育障碍的脑类器官中进行的药物筛选和药物重新定位研究进行了综述。本范围综述将总结研究脑类器官线粒体功能和动力学的局限性的证据。版权所有 © 2024 Coronel、García-Moreno、Siendones、Barrero、Martínez-Delgado、Santos-Ocaña 和 Cascajo-Almenara。

Mitochondrial diseases are a group of severe pathologies that cause complex neurodegenerative disorders for which, in most cases, no therapy or treatment is available. These organelles are critical regulators of both neurogenesis and homeostasis of the neurological system. Consequently, mitochondrial damage or dysfunction can occur as a cause or consequence of neurodevelopmental or neurodegenerative diseases. As genetic knowledge of neurodevelopmental disorders advances, associations have been identified between genes that encode mitochondrial proteins and neurological symptoms, such as neuropathy, encephalomyopathy, ataxia, seizures, and developmental delays, among others. Understanding how mitochondrial dysfunction can alter these processes is essential in researching rare diseases. Three-dimensional (3D) cell cultures, which self-assemble to form specialized structures composed of different cell types, represent an accessible manner to model organogenesis and neurodevelopmental disorders. In particular, brain organoids are revolutionizing the study of mitochondrial-based neurological diseases since they are organ-specific and model-generated from a patient's cell, thereby overcoming some of the limitations of traditional animal and cell models. In this review, we have collected which neurological structures and functions recapitulate in the different types of reported brain organoids, focusing on those generated as models of mitochondrial diseases. In addition to advancements in the generation of brain organoids, techniques, and approaches for studying neuronal structures and physiology, drug screening and drug repositioning studies performed in brain organoids with mitochondrial damage and neurodevelopmental disorders have also been reviewed. This scope review will summarize the evidence on limitations in studying the function and dynamics of mitochondria in brain organoids.Copyright © 2024 Coronel, García-Moreno, Siendones, Barrero, Martínez-Delgado, Santos-Ocaña and Cascajo-Almenara.