Doxaki Christina, Palikaras Konstantinos
General University Hospital of Heraklion, Crete, Greece.
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, Crete, Greece.
Front Cell Dev Biol. 2021 Jan 18;8:611938. doi: 10.3389/fcell.2020.611938. eCollection 2020.
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.
维持神经元内环境稳定是一项具有挑战性的任务，这是由于有丝分裂后神经元独特的细胞组织和生物能量需求。人们越来越认识到，线粒体稳态受损是神经元功能障碍的早期迹象，这在与年龄相关的神经退行性疾病以及神经发育障碍中都很常见。线粒体选择性自噬，即线粒体自噬，调节线粒体数量，以确保细胞对多种细胞内和环境刺激做出适应性反应。越来越多的证据表明，线粒体自噬水平的失调在神经退行性变过程中具有指导作用。虽然线粒体自噬的诱导介导了受损线粒体的清除并赋予神经保护作用，但不受控制的失控线粒体自噬可能会减少线粒体含量，使剩余的细胞器过度应激，最终引发神经元细胞死亡。揭示神经元线粒体自噬的分子机制及其在神经元存活和细胞死亡中的复杂作用，将有助于开发新型线粒体自噬调节剂，以促进健康和疾病状态下的细胞和机体稳态。
