Fig. 7

Impact of mitochondrial heterogeneity on cell fate. Systematic analysis of heterogeneity in Bax levels for mitochondrial population shows emergence of sub-populations. a (left) Single mitochondrion dose response to increasing tBid activation with (blue shaded) sub-population resistant to apoptosis stimuli. (middle) Histogram of mitochondrial population’s Bax level after randomly seeding each mitochondrion with Bax levels from Gaussian distributions (mean = 1, standard deviation = (0.1, 0.3, 0.6)), while keeping Bcl2 mean fixed (at 1). (blue shaded) emergence of small sub-population with very low Bax levels (right) Total number of mitochondria with mitophagy as final phenotype and total cytochrome c release for increasing Bax heterogeneity (b) Simulation of Bcl2 inhibition: Decreasing mean of anti-apoptotic Bcl2 (with s.d. = 0.1) while keeping the mean of Bax fixed (at 1) (c) Implementation of different combinations of heterogeneity in Bax and Bcl2 levels (see legend) compared to control (black line) at different stages of tBid activation (light green box is pre-tBid activation, dark green box is post-tBid activation). For all simulations sample size was 50 runs