Núñez-Vázquez Sonia, Saura-Esteller José, Sánchez-Vera Ismael, Guilbaud Emma, Cosialls Ana M, Pons Gabriel, Ricci Jean-Ehrland, Iglesias-Serret Daniel, Marchetti Sandrine, Gil Joan
Departament de Ciències Fisiològiques, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona, Oncobell-IDIBELL (Institut d'Investigació Biomèdica de Bellvitge), L'Hospitalet de Llobregat, Barcelona, Spain.
Université Côte d'Azur, INSERM, C3M, Nice, France.
Oncogenesis. 2021 Sep 27;10(9):64. doi: 10.1038/s41389-021-00352-9.
Fluorizoline is a prohibitin-binding compound that triggers apoptosis in several cell lines from murine and human origin, as well as in primary cells from hematologic malignancies by inducing the integrated stress response and ER stress. Recently, it was described that PHB (Prohibitin) 1 and 2 are crucial mitophagy receptors involved in mediating the autophagic degradation of mitochondria. We measured mitophagy in HeLa cells expressing Parkin and in A549, a lung cancer cell line that can undergo mitophagy in a Parkin-independent manner, and we demonstrated that both fluorizoline and rocaglamide A, another PHB-binding molecule, inhibit CCCP- and OA-induced mitophagy. Moreover, we demonstrated that PHBs are mediating Parkin-dependent mitophagy. In conclusion, besides being a potent pro-apoptotic compound, we present fluorizoline as a promising new mitophagy modulator that could be used as anticancer agent.
氟立唑啉是一种与 prohibitin 结合的化合物，可通过诱导整合应激反应和内质网应激在多种源自小鼠和人类的细胞系以及血液系统恶性肿瘤的原代细胞中引发凋亡。最近，有研究表明 PHB（prohibitin）1 和 2 是参与介导线粒体自噬降解的关键线粒体自噬受体。我们检测了表达 Parkin 的 HeLa 细胞以及 A549（一种可通过不依赖 Parkin 的方式进行线粒体自噬的肺癌细胞系）中的线粒体自噬，并且我们证明氟立唑啉和另一种与 PHB 结合的分子罗卡酰胺 A 均抑制 CCCP 和 OA 诱导的线粒体自噬。此外，我们证明 PHB 介导 Parkin 依赖性线粒体自噬。总之，除了是一种有效的促凋亡化合物外，我们还提出氟立唑啉是一种有前景的新型线粒体自噬调节剂，可作为抗癌剂使用。
