Popelka Hana, Uversky Vladimir N
Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Department of Molecular Medicine, Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Membranes (Basel). 2022 Apr 24;12(5):457. doi: 10.3390/membranes12050457.
Intrinsically disordered proteins and protein regions (IDPs/IDPRs) are mainly involved in signaling pathways, where fast regulation, temporal interactions, promiscuous interactions, and assemblies of structurally diverse components including membranes are essential. The autophagy pathway builds, de novo, a membrane organelle, the autophagosome, using carefully orchestrated interactions between proteins and lipid bilayers. Here, we discuss molecular mechanisms related to the protein disorder-based interactions of the autophagy machinery with membranes. We describe not only membrane binding phenomenon, but also examples of membrane remodeling processes including membrane tethering, bending, curvature sensing, and/or fragmentation of membrane organelles such as the endoplasmic reticulum, which is an important membrane source as well as cargo for autophagy. Summary of the current state of knowledge presented here will hopefully inspire new studies. A profound understanding of the autophagic protein-membrane interface is essential for advancements in therapeutic interventions against major human diseases, in which autophagy is involved including neurodegeneration, cancer as well as cardiovascular, metabolic, infectious, musculoskeletal, and other disorders.
内在无序蛋白和蛋白区域（IDPs/IDPRs）主要参与信号通路，在这些通路中，快速调节、瞬时相互作用、混杂相互作用以及包括膜在内的结构多样的组分的组装至关重要。自噬途径利用蛋白质与脂质双层之间精心编排的相互作用，从头构建一个膜细胞器——自噬体。在此，我们讨论与自噬机制基于蛋白质无序的与膜相互作用相关的分子机制。我们不仅描述膜结合现象，还描述膜重塑过程的实例，包括膜系留、弯曲、曲率感知和/或膜细胞器（如内质网，它是自噬的重要膜来源和货物）的碎片化。这里呈现的当前知识状态总结有望激发新的研究。深入了解自噬蛋白 - 膜界面对于针对主要人类疾病的治疗干预进展至关重要，这些疾病包括神经退行性疾病、癌症以及心血管、代谢、感染、肌肉骨骼和其他疾病，自噬均参与其中。
