{"title":"Protein aggregation and biomolecular condensation in hypoxic environments (Review).","authors":"Chaoqun Li, Bingjie Hao, Haiguang Yang, Kai Wang, Lihong Fan, Weihua Xiao","doi":"10.3892/ijmm.2024.5357","DOIUrl":null,"url":null,"abstract":"<p><p>Due to molecular forces, biomacromolecules assemble into liquid condensates or solid aggregates, and their corresponding formation and dissolution processes are controlled. Protein homeostasis is disrupted by increasing age or environmental stress, leading to irreversible protein aggregation. Hypoxic pressure is an important factor in this process, and uncontrolled protein aggregation has been widely observed in hypoxia‑related conditions such as neurodegenerative disease, cardiovascular disease, hypoxic brain injury and cancer. Biomolecular condensates are also high‑order complexes assembled from macromolecules. Although they exist in different phase from protein aggregates, they are in dynamic balance under certain conditions, and their activation or assembly are considered as important regulatory processes in cell survival with hypoxic pressure. Therefore, a better understanding of the relationship between hypoxic stress, protein aggregation and biomolecular condensation will bring marked benefits in the clinical treatment of various diseases. The aim of the present review was to summarize the underlying mechanisms of aggregate assembly and dissolution induced by hypoxic conditions, and address recent breakthroughs in understanding the role of aggregates in hypoxic‑related diseases, given the hypotheses that hypoxia induces macromolecular assemblage changes from a liquid to a solid phase, and that adenosine triphosphate depletion and ATP‑driven inactivation of multiple protein chaperones play important roles among the process. Moreover, it is anticipated that an improved understanding of the adaptation in hypoxic environments could extend the overall survival of patients and provide new strategies for hypoxic‑related diseases.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":null,"pages":null},"PeriodicalIF":8.3000,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903932/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Materials & Interfaces","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3892/ijmm.2024.5357","RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/16 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Due to molecular forces, biomacromolecules assemble into liquid condensates or solid aggregates, and their corresponding formation and dissolution processes are controlled. Protein homeostasis is disrupted by increasing age or environmental stress, leading to irreversible protein aggregation. Hypoxic pressure is an important factor in this process, and uncontrolled protein aggregation has been widely observed in hypoxia‑related conditions such as neurodegenerative disease, cardiovascular disease, hypoxic brain injury and cancer. Biomolecular condensates are also high‑order complexes assembled from macromolecules. Although they exist in different phase from protein aggregates, they are in dynamic balance under certain conditions, and their activation or assembly are considered as important regulatory processes in cell survival with hypoxic pressure. Therefore, a better understanding of the relationship between hypoxic stress, protein aggregation and biomolecular condensation will bring marked benefits in the clinical treatment of various diseases. The aim of the present review was to summarize the underlying mechanisms of aggregate assembly and dissolution induced by hypoxic conditions, and address recent breakthroughs in understanding the role of aggregates in hypoxic‑related diseases, given the hypotheses that hypoxia induces macromolecular assemblage changes from a liquid to a solid phase, and that adenosine triphosphate depletion and ATP‑driven inactivation of multiple protein chaperones play important roles among the process. Moreover, it is anticipated that an improved understanding of the adaptation in hypoxic environments could extend the overall survival of patients and provide new strategies for hypoxic‑related diseases.
在分子力的作用下,生物大分子会聚集成液态凝聚体或固态聚集体,并控制其相应的形成和溶解过程。随着年龄的增长或环境压力的增加,蛋白质的平衡会被打破,从而导致不可逆的蛋白质聚集。缺氧压力是这一过程中的一个重要因素,在神经退行性疾病、心血管疾病、缺氧性脑损伤和癌症等与缺氧有关的疾病中,已广泛观察到不受控制的蛋白质聚集。生物分子凝聚体也是由大分子组装而成的高阶复合物。虽然它们与蛋白质聚集体的存在阶段不同,但在特定条件下它们处于动态平衡状态,它们的激活或组装被认为是细胞在缺氧压力下生存的重要调节过程。因此,更好地理解缺氧压力、蛋白质聚集和生物分子凝结之间的关系,将为各种疾病的临床治疗带来显著的益处。本综述旨在总结缺氧条件下诱导的聚集体组装和溶解的基本机制,并探讨最近在理解聚集体在缺氧相关疾病中的作用方面取得的突破,其假说是缺氧诱导大分子组装从液相变为固相,而三磷酸腺苷耗竭和 ATP 驱动的多种蛋白伴侣失活在这一过程中发挥了重要作用。此外,对缺氧环境适应性的进一步了解有望延长患者的总体生存期,并为缺氧相关疾病的治疗提供新策略。
期刊介绍:
ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.