title: Depletion of mitochondrial fission factor DRP1 causes increased apoptosis in human colon cancer cells.
abstract: Mitochondria play a critical role in regulation of apoptosis, a form of programmed cell death, by releasing apoptogenic factors including cytochrome c. Growing evidence suggests that dynamic changes in mitochondrial morphology are involved in cellular apoptotic response. However, whether DRP1-mediated mitochondrial fission is required for induction of apoptosis remains speculative. Here, we show that siRNA-mediated DRP1 knockdown promoted accumulation of elongated mitochondria in HCT116 and SW480 human colon cancer cells. Surprisingly, DRP1 down-regulation led to decreased proliferation and increased apoptosis of these cells. A higher rate of cytochrome c release and reductions in mitochondrial membrane potential were also revealed in DRP1-depleted cells. Taken together, our present findings suggest that mitochondrial fission factor DRP1 inhibits colon cancer cell apoptosis through the regulation of cytochrome c release and mitochondrial membrane integrity.
authors.affiliation: Department of Pathology, Tokyo Women's Medical University, Tokyo 162-8666, Japan. ainoyama@research.twmu.ac.jp
authors.forename: Akane
authors.initials: A
authors.lastname: Inoue-Yamauchi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Oda
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000201:enzymology / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C533267:Mff protein, human; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D045304:Cytochromes c; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins