The effects of UV light on the skin have been extensively investigated. However, systematic information about how exposure to UVA light, the least energetic but the most abundant UV radiation reaching the Earth, shapes the subcellular organization of proteins is lacking. Using subcellular fractionation, mass spectrometry-based proteomics, machine learning algorithms, immunofluorescence, and functional assays, we mapped the subcellular reorganization of the proteome of human keratinocytes in response to UVA light. Our workflow quantified and assigned subcellular localization for over 1600 proteins, of which about 200 were found to redistribute upon UVA exposure. Reorganization of the proteome affected modulators of signaling pathways, cellular metabolism, and DNA damage response. Strikingly, mitochondria were identified as one of the main targets of UVA-induced stress. Further investigation demonstrated that UVA induces mitochondrial fragmentation, up-regulates redox-responsive proteins and attenuates respiratory rates. These observations emphasize the role of this radiation as a potent metabolic stressor in the skin.

中文翻译：

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空间蛋白质组学揭示暴露于 UVA 光的人类角质形成细胞的亚细胞重组

紫外线对皮肤的影响已被广泛研究。然而，关于暴露于 UVA 光（到达地球的能量最少但最丰富的紫外线辐射）如何塑造蛋白质的亚细胞组织的系统信息仍然缺乏。使用亚细胞分离、基于质谱的蛋白质组学、机器学习算法、免疫荧光和功能测定，我们绘制了人类角质形成细胞蛋白质组响应 UVA 光的亚细胞重组。我们的工作流程量化并分配了超过 1600 种蛋白质的亚细胞定位，其中约 200 种被发现在 UVA 暴露后重新分布。蛋白质组的重组影响信号通路、细胞代谢和 DNA 损伤反应的调节剂。引人注目的是，线粒体被确定为 UVA 诱导的应激的主要目标之一。进一步的研究表明，UVA 诱导线粒体断裂，上调氧化还原反应蛋白并降低呼吸频率。这些观察结果强调了这种辐射在皮肤中作为一种有效的代谢压力源的作用。