Maintenance of neuronal homeostasis is a challenging task, due to unique cellular organization and bioenergetic demands of post-mitotic neurons. It is increasingly appreciated that impairment of mitochondrial homeostasis represents an early sign of neuronal dysfunction that is common in both age-related neurodegenerative as well as in neurodevelopmental disorders. Mitochondrial selective autophagy, known as mitophagy, regulates mitochondrial number ensuring cellular adaptation in response to several intracellular and environmental stimuli. Mounting evidence underlines that deregulation of mitophagy levels has an instructive role in the process of neurodegeneration. Although mitophagy induction mediates the elimination of damaged mitochondria and confers neuroprotection, uncontrolled runaway mitophagy could reduce mitochondrial content overstressing the remaining organelles and eventually triggering neuronal cell death. Unveiling the molecular mechanisms of neuronal mitophagy and its intricate role in neuronal survival and cell death, will assist in the development of novel mitophagy modulators to promote cellular and organismal homeostasis in health and disease.

由于有丝分裂后神经元的独特细胞组织和生物能需求，维持神经元稳态是一项艰巨的任务。人们越来越认识到，线粒体稳态障碍代表了神经元功能障碍的早期迹象，这在年龄相关的神经退行性疾病和神经发育障碍中都很常见。线粒体选择性自噬（称为线粒体）调节线粒体数量，从而确保细胞对几种细胞内和环境刺激做出反应。越来越多的证据表明，线粒体水平的失控在神经变性过程中具有指导作用。尽管线粒体诱导介导消除了受损的线粒体并赋予了神经保护作用，失控的线粒体失控可减少线粒体含量，使剩余细胞器过度紧张，并最终触发神经元细胞死亡。揭示神经元线粒体的分子机制及其在神经元存活和细胞死亡中的复杂作用，将有助于新型线粒体调节剂的开发，以促进健康和疾病中的细胞和机体稳态。