Figure 4.

Selective fusion implies intermediate fusion rates are optimal for mutant clearance, whereas selective mitophagy implies complete fission is optimal. Numerical exploration of the shift in mean heteroplasmy for varying fusion:fission ratio, across different selectivity strengths. Stochastic simulations for mean heteroplasmy, evaluated at 1000 days, with an initial condition of $h=0.3$ and $n=1000$; the state was initialized on the steady-state line for the case of ${\mathit{ϵ}}_f={\mathit{ϵ}}_m=0$, for ${10}^4$ iterations. (A) For selective fusion (see Equation 15), for each value of fusion selectivity $\left({\mathit{ϵ}}_f\right)$, the fusion rate (γ) was varied relative to the nominal parameterization (see Table S2). When ${\mathit{ϵ}}_f>0$, the largest reduction in mean heteroplasmy occurs at intermediate values of the fusion rate; a deterministic treatment reveals this to be true for all fusion selectivities investigated (see Figure S7). (B) For selective mitophagy (see Equation 16), when mitophagy selectivity ${\mathit{ϵ}}_m>0$, a lower mean heteroplasmy is achieved and the lower the fusion rate (until mean heteroplasmy = 0 is achieved). Hence, complete fission is the optimal strategy for selective mitophagy.