Selective Autophagy Receptor p62/SQSTM1, a Pivotal Player in Stress and Aging.
Selective Autophagy Receptor p62/SQSTM1, a Pivotal Player in Stress and Aging.
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DOI：
10.3389/fcell.2022.793328
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发表时间：
2022
影响因子：
5.5
通讯作者：
Lapierre LR
中科院分区：
文献类型：
--
作者：
Kumar AV;Mills J;Lapierre LR
有效的蛋白质平衡对体细胞维持至关重要，其在衰老过程中的下降导致细胞功能障碍和疾病。选择性自噬是一种由受体介导的自噬形式，它针对特定的货物进行降解，是维持蛋白质稳态的重要过程。蛋白Sequestosome 1 （p62/SQSTM1）是一种经典的选择性自噬受体，但它也在泛素-蛋白酶体系统、细胞代谢、信号传导和凋亡中发挥作用。P62最为人所知的作用是通过聚集性清除蛋白质聚集体，但它最近被发现是其他形式的选择性自噬的受体，如有丝自噬和脂噬。值得注意的是，p62对机体衰老具有环境依赖性影响，p62的周转通常反映活跃的蛋白质静止。在这篇综述中，我们重点介绍了p62在协调泛素-蛋白酶体系统和自噬中的作用的最新进展。我们还讨论了p62对蛋白质抑制状态的积极和消极影响及其对衰老和神经变性的影响。最后，我们将p62缺陷与衰老疾病之间的联系联系起来，并研究了靶向这种多面蛋白以获得蛋白质抑制益处的效用。
Efficient proteostasis is crucial for somatic maintenance, and its decline during aging leads to cellular dysfunction and disease. Selective autophagy is a form of autophagy mediated by receptors that target specific cargoes for degradation and is an essential process to maintain proteostasis. The protein Sequestosome 1 (p62/SQSTM1) is a classical selective autophagy receptor, but it also has roles in the ubiquitin-proteasome system, cellular metabolism, signaling, and apoptosis. p62 is best known for its role in clearing protein aggregates via aggrephagy, but it has recently emerged as a receptor for other forms of selective autophagy such as mitophagy and lipophagy. Notably, p62 has context-dependent impacts on organismal aging and turnover of p62 usually reflects active proteostasis. In this review, we highlight recent advances in understanding the role of p62 in coordinating the ubiquitin-proteasome system and autophagy. We also discuss positive and negative effects of p62 on proteostatic status and their implications on aging and neurodegeneration. Finally, we relate the link between defective p62 and diseases of aging and examine the utility of targeting this multifaceted protein to achieve proteostatic benefits.
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影响因子：
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作者：
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