Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China.
Center for Drug Safety Evaluation and Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
Neurochem Int. 2022 Jan;152:105253. doi: 10.1016/j.neuint.2021.105253. Epub 2021 Dec 2.
Mitophagy controls mitochondrial quality to maintain cellular homeostasis, while aberrations in this process are responsible for neurodegenerative diseases. Mitophagy is initiated through the recruitment of autophagosomes in a ubiquitin-dependent or ubiquitin-independent manner under different stress conditions. Although the detailed molecular mechanisms of how mitophagy processes influence neurodegeneration remain largely uncharacterized, there is mounting evidence indicating that non-coding RNAs (ncRNAs), a variety of endogenous regulators, including microRNAs and long non-coding RNAs, extensively participate in mitophagy processes and play pivotal roles in the aging process and neurodegenerative diseases. Here, we reviewed the major mitophagy pathways modulated by some classical and newly found ncRNAs and summarized the diverse mechanisms in a regulatory network. We also discussed the generalizability of ncRNAs in the development of common neurodegenerative diseases related to proteotoxicity and the importance of mitophagy in the pathogenesis of these diseases. In summary, we propose that ncRNAs act as linkers between mitophagy and neurodegeneration, showing the potential therapeutic application of mitophagy regulation mediated by ncRNAs in neurodegenerative diseases.
自噬控制线粒体的质量以维持细胞内稳态，而该过程的异常是导致神经退行性疾病的原因。自噬是在不同的应激条件下通过泛素依赖性或非依赖性方式募集自噬体来启动的。虽然自噬过程影响神经退行性变的详细分子机制在很大程度上仍未被阐明，但越来越多的证据表明，非编码 RNA（ncRNA），包括 microRNAs 和长非编码 RNA 等多种内源性调节剂，广泛参与自噬过程，并在衰老过程和神经退行性疾病中发挥关键作用。在这里，我们综述了一些经典和新发现的 ncRNA 调节的主要自噬途径，并总结了调控网络中的不同机制。我们还讨论了 ncRNA 在与蛋白毒性相关的常见神经退行性疾病发展中的普遍性以及自噬在这些疾病发病机制中的重要性。总之，我们提出 ncRNA 作为自噬和神经退行性变之间的联系，表明 ncRNA 介导的自噬调节在神经退行性疾病中的潜在治疗应用。
