Normal brain functioning relies on high aerobic energy production provided by mitochondria. Failure to supply a sufficient amount of energy, seen in different brain disorders, including autism spectrum disorder (ASD), may have a significant negative impact on brain development and support of different brain functions. Mitochondrial dysfunction, manifested in the abnormal activities of the electron transport chain and impaired energy metabolism, greatly contributes to ASD. The aberrant functioning of this organelle is of such high importance that ASD has been proposed as a mitochondrial disease. It should be noted that aerobic energy production is not the only function of the mitochondria. In particular, these organelles are involved in the regulation of Ca²⁺ homeostasis, different mechanisms of programmed cell death, autophagy, and reactive oxygen and nitrogen species (ROS and RNS) production. Several syndromes originated from mitochondria-related mutations display ASD phenotype. Abnormalities in Ca²⁺ handling and ATP production in the brain mitochondria affect synaptic transmission, plasticity, and synaptic development, contributing to ASD. ROS and Ca²⁺ regulate the activity of the mitochondrial permeability transition pore (mPTP). The prolonged opening of this pore affects the redox state of the mitochondria, impairs oxidative phosphorylation, and activates apoptosis, ultimately leading to cell death. A dysregulation between the enhanced mitochondria-related processes of apoptosis and the inhibited autophagy leads to the accumulation of toxic products in the brains of individuals with ASD. Although many mitochondria-related mechanisms still have to be investigated, and whether they are the cause or consequence of this disorder is still unknown, the accumulating data show that the breakdown of any of the mitochondrial functions may contribute to abnormal brain development leading to ASD. In this review, we discuss the multifaceted role of mitochondria in ASD from the various aspects of neuroscience.

正常的大脑功能依赖于线粒体提供的高有氧能量产生。未能提供足够的能量，见于不同的大脑疾病，包括自闭症谱系障碍 （ASD），可能会对大脑发育和不同大脑功能的支持产生重大的负面影响。线粒体功能障碍表现为电子传递链活动异常和能量代谢受损，是 ASD 的重要原因。这种细胞器的异常功能非常重要，以至于 ASD 已被提议作为一种线粒体疾病。应该注意的是，有氧能量的产生并不是线粒体的唯一功能。特别是，这些细胞器参与 Ca²⁺ 稳态的调节、程序性细胞死亡的不同机制、自噬以及活性氧和氮物质 （ROS 和 RNS） 的产生。几种起源于线粒体相关突变的综合征显示 ASD 表型。大脑线粒体中 Ca²⁺ 处理和 ATP 产生的异常会影响突触传递、可塑性和突触发育，从而导致 ASD。ROS 和 Ca²⁺ 调节线粒体通透性转换孔 （mPTP） 的活性。该孔的长时间开放会影响线粒体的氧化还原状态，损害氧化磷酸化，并激活细胞凋亡，最终导致细胞死亡。增强的线粒体相关细胞凋亡过程与抑制的自噬之间的失调导致有毒产物在 ASD 个体的大脑中积累。 尽管许多与线粒体相关的机制仍需调查，并且它们是这种疾病的原因还是后果仍是未知数，但不断积累的数据表明，任何线粒体功能的崩溃都可能导致大脑发育异常，从而导致 ASD。在这篇综述中，我们从神经科学的各个方面讨论了线粒体在 ASD 中的多方面作用。