Fig. 3

Impact of mitophagy/apoptosis signaling and ROS production on homogeneous mitochondrial population. Autophagic vesicles are randomly distributed to cover 20 % of cell surface (AV = 75) with a population of 100 mitochondria seeded with equal initial content (Bnip3 = 1, Bcl2 = 1, Bax = 1). All simulations are run for 100 time steps and sample size of 50 runs. a In absence of tBid activation and with 20 % pre-activation of Bnip3 LIR activity, scatter points (blue) track mitochondrial content individually, with size and color depth indicating level of mitophagy potential at every time step. Total mitophagic content in mitochondrial population (blue line) indicates the population response. The population exhibits three phases (insets): activation of signaling pathways (light gray), competition to commit to a phenotype (dark gray), and a committed phase during which phenotype is executed (olive). Runs show cell-to-cell variability (blue shaded area). Tables indicate statistics of total mitophagy potential after 30 time steps around the time of phenotype commitment, with sample size of 50 runs. b With tBid activation at t = 5 following 20 % pre-activation of Bnip3 LIR activity shows total apoptotic potential (red line) and total mitophagy potential (blue line). Scatter points track mitochondrial content individually showing mitophagy (blue) or apoptosis (red) potential at every time step. (Inset top) Final phenotype of all mitochondria shows size of mitophagy (blue) and apoptosis (red) sub-populations, and consequent cytochrome c release (green). Tables show statistics after 50 time steps, sampled over 50 runs. c Example simulation images (at t = 30) of 20 % pre-activation of Bnip3 followed by tBid activation (at t = 5), showing mitochondrial sub-populations with mitophagy (blue) or apoptosis (red) phenotypes and cytochrome c release environment layer (green); merged (black background)