The heat shock response (HSR) is a conserved cellular defensive response against stresses such as temperature, oxidative stress and heavy metals. A significant group of players in the HSR is the set of molecular chaperones known as heat shock proteins (HSPs), which assist in the refolding of unfolded proteins and prevent the accumulation of damaged proteins. HSP genes are activated by the HSF1 transcription factor, a master regulator of the HSR pathway. A variety of stressors activate HSF1, but the key molecular players and the processes that directly contribute to HSF1 activation remain unclear. In this study, we show that heat shock induces perinuclear clustering of mitochondria in mammalian cells, and this clustering is essential for activation of the HSR. We also show that this perinuclear clustering of mitochondria results in increased levels of reactive oxygen species in the nucleus, leading to the activation of hypoxia-inducible factor-1α (HIF-1α). To conclude, we provide evidence to suggest that HIF-1α is one of the crucial regulators of HSF1 and that HIF-1α is essential for activation of the HSR during heat shock.

热休克反应（HSR）是针对温度、氧化应激和重金属等应激的保守细胞防御反应。HSR 中的一个重要参与者是一组称为热休克蛋白 (HSP) 的分子伴侣，它们有助于未折叠蛋白质的重新折叠并防止受损蛋白质的积累。HSP 基因由 HSF1 转录因子激活，HSF1 转录因子是 HSR 途径的主要调节因子。多种应激源可激活 HSF1，但直接促进 HSF1 激活的关键分子参与者和过程仍不清楚。在这项研究中，我们发现热休克会诱导哺乳动物细胞中线粒体的核周聚集，而这种聚集对于 HSR 的激活至关重要。我们还表明，线粒体的核周聚集导致细胞核中活性氧水平增加，从而激活缺氧诱导因子 1α (HIF-1α)。总之，我们提供的证据表明 HIF-1α 是 HSF1 的关键调节因子之一，并且 HIF-1α 对于热休克期间 HSR 的激活至关重要。