title: Bax is essential for Drp1-mediated mitochondrial fission but not for mitochondrial outer membrane permeabilization caused by photodynamic therapy.
abstract: Bcl-2 family proteins are critical for the regulation of apoptosis, with the pro-apoptotic members Bax essential for the release of cytochrome c from mitochondria in many instances. However, we found that Bax was activated after mitochondrial depolarization and the completion of cytochrome c release induced by photodynamic therapy (PDT) with the photosensitizer Photofrin in human lung adenocarcinoma cells (ASTC-a-1). Besides, knockdown of Bax expression by gene silencing had no effect on mitochondrial depolarization and cytochrome c release, indicating that Bax makes no contribution to mitochondrial outer membrane permeabilization (MOMP) following PDT. Further study revealed that Bax knockdown only slowed down the speed of cell death induced by PDT, indicating that Bax is not essential for PDT-induced apoptosis. The fact that Bax knockdown totally inhibited the mitochondrial accumulation of dynamin-related protein (Drp1) and Drp1 knockdown attenuated cell apoptosis suggest that Bax can promote PDT-induced apoptosis through promoting Drp1 activation. Besides, Drp1 knockdown also failed to inhibit PDT-induced cell death finally, indicating that Bax-mediated Drp1's mitochondrial translocation is not essential for PDT-induced cell apoptosis. On the other hand, we found that protein kinase Cδ (PKCδ), Bim L and glycogen synthase kinase 3β (GSK3β) were activated upon PDT treatment and might contribute to the activation of Bax under the condition. Taken together, Bax activation is not essential for MOMP but essential for Drp1-mediated mitochondrial fission during the apoptosis caused by Photofrin-PDT.
authors.affiliation: MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Wu
authors.forename: Feifan
authors.initials: F
authors.lastname: Zhou
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Da
authors.initials: D
authors.lastname: Xing
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability / Q000528:radiation effects*; D017323:Dihematoporphyrin Ether / Q000494:pharmacology; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D024101:Mitochondrial Proteins / Q000378:metabolism*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D017319:Photosensitizing Agents; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein; D017323:Dihematoporphyrin Ether; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins