Mitochondrial levels determine variability in cell death by modulating apoptotic gene expression.

ABSTRACT: 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 mitochondri

SUBMITTER: Marquez-Jurado S 

PROVIDER: S-EPMC5785974 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature