Mitochondrial levels determine variability in cell death by modulating apoptotic gene expression
| Autor: | Raúl Guantes, Juan Diaz-Colunga, Antonio Martinez-Lorente, Fernando Almazán, Ricardo Pires das Neves, Silvia Márquez-Jurado, Francisco J. Iborra |
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| Přispěvatelé: | UAM. Departamento de Física de la Materia Condensada, UAM. Centro de Investigación en Fisica de la Materia Condensada (IFIMAC), UAM. Instituto Universitario de Ciencia de Materiales Nicolás Cabrera (INC), Universidad de Alicante. Departamento de Biotecnología, Biotecnología |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Cell death
0301 basic medicine Programmed cell death Cancer cells Science Regulator Gene Expression General Physics and Astronomy Apoptosis Biología Celular Biology Mitochondrion Article General Biochemistry Genetics and Molecular Biology TNF-Related Apoptosis-Inducing Ligand HeLa 03 medical and health sciences Protein levels Gene expression Humans Variability Apoptotic gene expression lcsh:Science Mitochondrial levels Multidisciplinary Cell Death Models Genetic Física General Chemistry biology.organism_classification Mitochondria 3. Good health Cell biology Mitochondrial Death 030104 developmental biology Cancer cell lcsh:Q Apoptotic Signal transduction Apoptosis Regulatory Proteins Reactive Oxygen Species Algorithms HeLa Cells Signal Transduction |
| Zdroj: | Biblos-e Archivo. Repositorio Institucional de la UAM instname Biblos-e Archivo: Repositorio Institucional de la UAM Universidad Autónoma de Madrid Nature Communications, Vol 9, Iss 1, Pp 1-11 (2018) Nature Communications RUA. Repositorio Institucional de la Universidad de Alicante Universidad de Alicante (UA) |
| DOI: | 10.1038/s41467-017-02787-4 |
| Popis: | Fractional killing is the main cause of tumour resistance to chemotherapy. This phenomenon is observed even in genetically identical cancer cells in homogeneous microenvironments. To understand this variable resistance, here we investigate the individual responses to TRAIL in a clonal population of HeLa cells using live-cell microscopy and computational modelling. We show that the cellular mitochondrial content determines the apoptotic fate and modulates the time to death, cells with higher mitochondrial content are more prone to die. We find that all apoptotic protein levels are modulated by the mitochondrial content. Modelling the apoptotic network, we demonstrate that these correlations, and especially the differential control of anti- and pro-apoptotic protein pairs, confer mitochondria a powerful discriminatory capacity of apoptotic fate. We find a similar correlation between the mitochondria and apoptotic proteins in colon cancer biopsies. Our results reveal a different role of mitochondria in apoptosis as the global regulator of apoptotic protein expression. It is unclear what causes variation in cell death in response to chemotherapy. Here, the authors show that cellular mitochondrial content modulates apoptotic protein levels, which in turn regulates response to agents such as TRAIL. |
| Databáze: | OpenAIRE |
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