Cyanobacterial blooms, usually dominated by Microcystis aeruginosa, pose a serious threat to global freshwater ecosystems owing to their production and release of various harmful secondary metabolites. Detection of the chemicals in M. aeruginosa exudates using metabolomics technology revealed that phytosphingosine (PHS) was one of the most abundant compounds. However, its specific toxicological mechanism remained unclear. CNE-2 cells were selected to illustrate the cytotoxic mechanism of PHS, and it was determined to cause excessive production of reactive oxygen species and subsequently damage the mitochondrial structure. Mitochondrial membrane rupture led to matrix mitochondrial membrane potential disintegration, which induced Ca²⁺ overload and interrupted ATP synthesis. Furthermore, rupture of the mitochondrial membrane induced the opening of the permeability transition pore, which caused the release of proapoptotic factors into the cytoplasm and the expression of apoptosis-related proteins Bax, Bcl-2, cytochrome-c and cleaved caspase-3 in CNE-2 cells. These events, in turn, activated the mitochondrially mediated intrinsic apoptotic pathway. A mitochondrial repair mechanism, namely, PINK1/Parkin-mediated mitophagy, was then blocked, which further promoted apoptosis. Our findings suggest that more attention should be paid to the ecotoxicity of PHS, which is already listed as a contaminant of emerging concern.

蓝藻水华，通常以铜绿微囊藻为主，由于其产生和释放各种有害的次生代谢物，对全球淡水生态系统构成严重威胁。使用代谢组学技术检测绿脓杆菌分泌物中的化学物质表明，植物鞘氨醇 (PHS) 是最丰富的化合物之一。然而，其具体毒理机制仍不清楚。选择 CNE-2 细胞来说明 PHS 的细胞毒性机制，并确定它会导致活性氧物质的过量产生并随后破坏线粒体结构。线粒体膜破裂导致基质线粒体膜电位崩解，从而诱导 Ca ²⁺过载和中断 ATP 合成。此外，线粒体膜破裂诱导通透性转换孔打开，导致促凋亡因子释放到细胞质中，CNE中凋亡相关蛋白Bax、Bcl-2、细胞色素-c和cleaved caspase-3表达-2 个细胞。这些事件反过来又激活了线粒体介导的内在凋亡途径。然后阻断了线粒体修复机制，即 PINK1/Parkin 介导的线粒体自噬，这进一步促进了细胞凋亡。我们的研究结果表明，应该更多地关注 PHS 的生态毒性，它已经被列为新兴关注的污染物。