Department of Neurobiology and Collaborative Innovation Center for Brain Science, School of Basic Medicine, Fourth Military Medical University, No. 169 Changle West Road, Xi'an, 710032, People's Republic of China.
Cadet Brigade, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
J Bioenerg Biomembr. 2017 Oct;49(5):413-422. doi: 10.1007/s10863-017-9727-7. Epub 2017 Oct 3.
P62, also called sequestosome1 (SQSTM1), is the selective cargo receptor for autophagy to degenerate misfolded proteins. It has also been found to assist and connect parkin in pink1/parkin mitophagy pathway. Previous studies showed that p62 was in association with neurodegenerative diseases, and one of the diseases pathogenesis is P62 induced autophagy and mitophagy dysfunction. Autophagy is an important process to eliminate misfolded proteins. Intracellular aggregation including α-synuclein, Huntingtin, tau protein and ß-amyloid (Aß) protein are the misfolded proteins found in PD, HD and AD, respectively. P62 induced autophagy failure significantly accelerates misfolded protein aggregation. Mitophagy is the special autophagy, functions as the selective scavenger towards the impaired mitochondria. Mitochondrial dysfunction was confirmed greatly contribute to the occurrence of neurodegenerative diseases. Through assistance and connection with parkin, P62 is vital for regulating mitophagy, thus, aberrant P62 could influence the balance of mitophagy, and further disturb mitochondrial quality control. Therefore, accumulation of misfolded proteins leads to the aberrant P62 expression, aberrant P62 influence the balance of mitophagy, forming a vicious circle afterwards. In this review, we summarize the observations on the function of P62 relevant to autophagy and mitophagy in neurodegenerative diseases, hoping to give some clear and objective opinions to further study.
P62，也被称为自噬体相关蛋白 1（SQSTM1），是自噬作用选择性降解细胞内错误折叠蛋白的货物受体。它还被发现有助于并连接 parkin 蛋白参与到 pink1/parkin 介导的线粒体自噬途径中。先前的研究表明，P62 与神经退行性疾病有关，其中一种疾病的发病机制是 P62 诱导的自噬和线粒体自噬功能障碍。自噬是清除错误折叠蛋白的重要过程。细胞内聚集的包括α-突触核蛋白、亨廷顿蛋白、tau 蛋白和β-淀粉样蛋白（Aβ）蛋白，分别是 PD、HD 和 AD 中发现的错误折叠蛋白。P62 诱导的自噬失败显著加速了错误折叠蛋白的聚集。线粒体自噬是一种特殊的自噬，作为受损线粒体的选择性清除剂。线粒体功能障碍被证实极大地促成了神经退行性疾病的发生。通过与 parkin 蛋白的协助和连接，P62 对调节线粒体自噬至关重要，因此，异常的 P62 可能会影响线粒体自噬的平衡，并进一步扰乱线粒体质量控制。因此，错误折叠蛋白的积累导致异常 P62 的表达，异常 P62 影响线粒体自噬的平衡，随后形成一个恶性循环。在这篇综述中，我们总结了与神经退行性疾病中自噬和线粒体自噬相关的 P62 功能的观察结果，希望为进一步的研究提供一些清晰和客观的观点。
