Mitochondrial origins of fractional control in regulated cell death

• DOI: 10.1038/s41467-019-09275-x
• Publication Date: 2019-03-21T11:20:37Z
• Authors: Luís C. Santos; Robert Vogel; Jerry E. Chipuk; Marc R. Birtwistle; Gustavo Stolovitzky; Pablo Meyer
• Keywords: 0303 health sciences; Models, Genetic; Cell Survival; Science; Q; Genetic Variation; Apoptosis; Epithelial Cells; Article; Mitochondria; 3. Good health; Gene Expression Regulation, Neoplastic; TNF-Related Apoptosis-Inducing Ligand; Jurkat Cells; 03 medical and health sciences; bcl-2 Homologous Antagonist-Killer Protein; Cell Line, Tumor; Humans; Annexin A5; Organic Chemicals; Biomarkers; Fluorescent Dyes; HeLa Cells; bcl-2-Associated X Protein

Individual cells in clonal populations often respond differently to environmental changes; for binary phenotypes, such as cell death, this can be measured a fractional response. These types of responses have been attributed cell-intrinsic stochastic processes and variable abundances biochemical constituents, proteins, but the influence organelles is still under investigation. We use response TNF-related apoptosis inducing ligand (TRAIL) new statistical framework determining parameter on cell-to-cell variability through inference variance explained, DEPICTIVE, demonstrate that mitochondria abundance correlates with survival determines death By quantitative data analysis modeling we attribute effect effective concentrations at surface pro-apoptotic proteins Bax/Bak. Further, our study suggests inhibitors anti-apoptotic Bcl-2 family used cancer treatment, may increase diversity cellular responses, enhancing resistance treatment.