Mallouk Y, Vayssier-Taussat M, Bonventre J V, Polla B S
Laboratoire de Physiologie Respiratoire, Groupe Hospitalier et Universitaire Cochin-Port Royal, Universite Paris V, 75014 Paris, France.
Int J Mol Med. 1999 Nov;4(5):463-74. doi: 10.3892/ijmm.4.5.463.
Heat shock proteins (HSP) are molecular chaperones, involved in many cellular functions such as protein folding, transport, maturation and degradation. Since they control the quality of newly synthesized proteins, HSP take part in cellular homeostasis. The Hsp70 family in particular exerts these functions in an adenosine triphosphate (ATP)-dependent manner. ATP is the main energy source used by cells to assume fundamental functions (respiration, proliferation, differentiation, apoptosis). Therefore, ATP levels have to be adapted to the requirements of the cells and ATP generation must constantly compensate ATP consumption. Nevertheless, under particular stress conditions, ATP levels decrease, threatening cell homeostasis and integrity. Cells have developed adaptive and protective mechanisms, among which Hsp70 synthesis and overexpression. In this review, we focus on the mechanisms which regulate Hsp70 expression under ATP depletion, using ischaemia as a paradigmatic model for ATP depletion in vivo, and analyze the molecular targets for Hsp70-mediated protection against ATP depletion. We also consider how these Hsp70-mediated protective effects could be applied in the therapeutical approaches of human diseases associated with cellular ATP depletion.
热休克蛋白（HSP）是分子伴侣，参与许多细胞功能，如蛋白质折叠、转运、成熟和降解。由于它们控制新合成蛋白质的质量，HSP参与细胞内稳态。特别是Hsp70家族以三磷酸腺苷（ATP）依赖的方式发挥这些功能。ATP是细胞用于承担基本功能（呼吸、增殖、分化、凋亡）的主要能量来源。因此，ATP水平必须适应细胞的需求，并且ATP生成必须不断补偿ATP消耗。然而，在特定的应激条件下，ATP水平会降低，威胁细胞内稳态和完整性。细胞已经发展出适应性和保护机制，其中包括Hsp70的合成和过表达。在这篇综述中，我们以缺血作为体内ATP耗竭的典型模型，重点关注ATP耗竭时调节Hsp70表达的机制，并分析Hsp70介导的针对ATP耗竭的保护作用的分子靶点。我们还考虑了这些Hsp70介导的保护作用如何应用于与细胞ATP耗竭相关的人类疾病的治疗方法中。
