Figure 7. Mitochondrial infectious damage adaptation (MIDA) model.

Schematic representation showing the loss of mitochondrial quality over the fictive life span of an organism according to the MIDA model (green) versus a non-MIDA model (blue). In the MIDA model fusion–fission rates are reduced when a certain degree of molecular damage has accumulated (green arrow). In the non-MIDA model this adaptation was omitted. Stage I is characterized by high fusion–fission rates, low levels of accumulated random molecular damage, yet a high removal rate of those few dysfunctional mitochondria. Stage II represents the time/age when already a significant amount of molecular damage has accumulated. This damage is propagated and enhanced by ongoing fusion and fission cycles, representing a distinct type of damage, termed ‘infectious molecular damage’. At some time point the latter outweighs the benefit of mitochondrial dynamics and mitophagy in removing dysfunctional mitochondria. Decelerating mitochondrial dynamics (green arrow), in the MIDA model, slows down the accumulation of dysfunctional mitochondria compared to the situation in the non-MIDA model. Still, this adaptation in the MIDA model renders the system less capable of dealing with additional random molecular damage. Assuming a certain survival threshold (dotted line) this results in a net life span extension. Reaching this threshold marks stage III and cell death. The rates for mitophagy, quality decay, and mitochondrial biogenesis under homeostatic conditions are kept constant over all stages. The full simulation and used parameters are provided in the Supporting Information.