Defects in Mitochondrial Fission Protein Dynamin-Related Protein 1 Are Linked to Apoptotic Resistance and Autophagy in a Lung Cancer Model
| العنوان: | Defects in Mitochondrial Fission Protein Dynamin-Related Protein 1 Are Linked to Apoptotic Resistance and Autophagy in a Lung Cancer Model |
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| المؤلفون: | Marty R. Jacobson, Kelly Jean Thomas |
| المصدر: | PLoS ONE, Vol 7, Iss 9, p e45319 (2012) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Dynamins, Lung Neoplasms, Blotting, Western, lcsh:Medicine, Apoptosis, Enzyme-Linked Immunosorbent Assay, Bioenergetics, Biology, Biochemistry, Mitochondrial Dynamics, Mitochondrial apoptosis-induced channel, Lung and Intrathoracic Tumors, GTP Phosphohydrolases, Mitochondrial Proteins, DNM1L, Cell Line, Tumor, Molecular Cell Biology, Autophagy, Humans, lcsh:Science, Inner mitochondrial membrane, Energy-Producing Organelles, Multidisciplinary, Cell Death, Caspase 3, lcsh:R, Cancers and Neoplasms, Cytochromes c, Epithelial Cells, respiratory system, Molecular biology, Cellular Structures, Non-Small Cell Lung Cancer, Cell biology, Eukaryotic Cells, Subcellular Organelles, Oncology, Mitochondrial permeability transition pore, DNAJA3, Medicine, Apoptosis-inducing factor, lcsh:Q, Mitochondrial fission, ATP–ADP translocase, Cellular Types, Microtubule-Associated Proteins, Research Article |
| الوصف: | Evasion of apoptosis is implicated in almost all aspects of cancer progression, as well as treatment resistance. In this study, resistance to apoptosis was identified in tumorigenic lung epithelial (A549) cells as a consequence of defects in mitochondrial and autophagic function. Mitochondrial function is determined in part by mitochondrial morphology, a process regulated by mitochondrial dynamics whereby the joining of two mitochondria, fusion, inhibits apoptosis while fission, the division of a mitochondrion, initiates apoptosis. Mitochondrial morphology of A549 cells displayed an elongated phenotype-mimicking cells deficient in mitochondrial fission protein, Dynamin-related protein 1 (Drp1). A549 cells had impaired Drp1 mitochondrial recruitment and decreased Drp1-dependent fission. Cytochrome c release and caspase-3 and PARP cleavage were impaired both basally and with apoptotic stimuli in A549 cells. Increased mitochondrial mass was observed in A549 cells, suggesting defects in mitophagy (mitochondrial selective autophagy). A549 cells had decreased LC3-II lipidation and lysosomal inhibition suggesting defects in autophagy occur upstream of lysosomal degradation. Immunostaining indicated mitochondrial localized LC3 punctae in A549 cells increased after mitochondrial uncoupling or with a combination of mitochondrial depolarization and ectopic Drp1 expression. Increased inhibition of apoptosis in A549 cells is correlated with impeded mitochondrial fission and mitophagy. We suggest mitochondrial fission defects contribute to apoptotic resistance in A549 cells. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::55bf55cd0919d316e103e34f8111685cTest https://doi.org/10.1371/journal.pone.0045319Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....55bf55cd0919d316e103e34f8111685c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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