Valenti Daniela, Vacca Rosa Anna
Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council (CNR), Via G. Amendola 122/O, 70126 Bari, Italy.
Int J Mol Sci. 2023 Aug 6;24(15):12488. doi: 10.3390/ijms241512488.
Mitochondria, far beyond their prominent role as cellular powerhouses, are complex cellular organelles active as central metabolic hubs that are capable of integrating and controlling several signaling pathways essential for neurological processes, including neurogenesis and neuroplasticity. On the other hand, mitochondria are themselves regulated from a series of signaling proteins to achieve the best efficiency in producing energy, in establishing a network and in performing their own de novo synthesis or clearance. Dysfunctions in signaling processes that control mitochondrial biogenesis, dynamics and bioenergetics are increasingly associated with impairment in brain development and involved in a wide variety of neurodevelopmental disorders. Here, we review recent evidence proving the emerging role of mitochondria as master regulators of brain bioenergetics, highlighting their control skills in brain neurodevelopment and cognition. We analyze, from a mechanistic point of view, mitochondrial bioenergetic dysfunction as causally interrelated to the origins of typical genetic intellectual disability-related neurodevelopmental disorders, such as Down, Rett and Fragile X syndromes. Finally, we discuss whether mitochondria can become therapeutic targets to improve brain development and function from a holistic perspective.
线粒体，远不止是作为细胞动力源的突出作用，它们是复杂的细胞器，作为核心代谢枢纽发挥作用，能够整合和控制神经过程所必需的多种信号通路，包括神经发生和神经可塑性。另一方面，线粒体自身受一系列信号蛋白的调控，以在产生能量、建立网络以及进行自身的从头合成或清除方面实现最佳效率。控制线粒体生物发生、动力学和生物能量学的信号传导过程功能障碍，越来越多地与脑发育受损相关，并涉及多种神经发育障碍。在此，我们综述了近期证据，证明线粒体作为脑生物能量学主要调节因子的新作用，突出它们在脑神经发育和认知中的调控技能。我们从机制角度分析线粒体生物能量功能障碍与典型遗传性智力残疾相关神经发育障碍（如下丘脑、雷特和脆性X综合征）起源的因果关联。最后，我们从整体角度讨论线粒体是否可成为改善脑发育和功能的治疗靶点。
