FIG. 2.
The in-silico model simulated a population of mitochondria, each containing 10 copies of mitochondrial functional components (representing the mitochondrial DNA, protein, and lipids required to maintain mitochondrial respiratory function). Each copy was classified as either ‘‘intact’’ or ‘‘damaged’’ (nonfunctional). Mitochondria were subjected to a steady rate of random damage that irreversibly converted random copies from intact to damaged. Accordingly, the number of nondamaged copies was used to deduct the level of mitochondrial activity (Δψm equivalent) on a 0–1 scale for each mitochondrion in the cell. The plotted cellular mitochondrial activity is generated by summing the activity of 300 mitochondria in each individual cell and then averaging the 100 different cells that are simulated in parallel. Autophagy targets mitochondria with activity level below 0.3, which was found in the solitary phase, as giant mitochondria fail to fuse (14, 77). Selective (a) and nonselective (b) fusion are compared under low and high (fourfold higher) damage rates. Note that, under increased rates of damage, mitochondrial activity is severely reduced if fusion is nonselective. Dotted line in (b) indicates the “selective” case of fusion under low-damage rate shown in (a). Gray bars indicate the physiological range of mitochondrial fusion in INS1 mitochondria under normal conditions. Data are modified from Mouli et al. (72).