Valerio Hellen Paula, Ravagnani Felipe Gustavo, Yaya Candela Angela Paola, Dias Carvalho da Costa Bruna, Ronsein Graziella Eliza, Di Mascio Paolo
Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo 05508-000, Brazil.
iScience. 2022 Mar 16;25(4):104093. doi: 10.1016/j.isci.2022.104093. eCollection 2022 Apr 15.
The effects of UV light on the skin have been extensively investigated. However, systematic information about how the exposure to ultraviolet-A (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 1,600 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.
紫外线对皮肤的影响已得到广泛研究。然而，关于暴露于紫外线A（UVA）——到达地球的能量最低但最丰富的紫外线辐射——如何塑造蛋白质的亚细胞组织，目前还缺乏系统的信息。我们运用亚细胞分级分离、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，绘制了人类角质形成细胞蛋白质组在UVA照射下的亚细胞重组图谱。我们的工作流程对1600多种蛋白质的亚细胞定位进行了量化和分配，其中约200种蛋白质在UVA照射后发生重新分布。蛋白质组的重组影响了信号通路、细胞代谢和DNA损伤反应的调节因子。值得注意的是，线粒体被确定为UVA诱导应激的主要靶点之一。进一步研究表明，UVA诱导线粒体碎片化，上调氧化还原反应蛋白，并降低呼吸速率。这些观察结果强调了这种辐射作为皮肤中一种强大的代谢应激源的作用。
