Fig 2. Intermediate heteroplasmies can be less efficient than either wildtype or mutant homoplasmy.

A visualization of the cost function in (w, m) space is shown for both saturating and linear output models, for various mutant pathologies (described by ϵ₁). For visualization purposes, states in which cellular demand cannot be satisified are shown in white. Cells in these states may still survive by e.g. increasing glycolysis (effectively reducing mitochondrial demand). This figure assumes high copy numbers, results are qualitatively similar for low copy numbers. The actual cost values (given by the colour map) are of lesser importance for our findings, we rather focus on the qualitative shape of the cost function. A: The magenta (solid) and black (dashed) lines show the contour of the demand-satisfying region when demand is increased by 10%, or demand is increased by 50% and cellular resource availability is increased by 35%, respectively. B: The orange line corresponds to constant total copy number; moving up along this line increases heteroplasmy. Cells in region 1 or region 3 are more efficient, and show a lower cost, than cells in region 2. C: The linear mitochondrial output model does not show a decreased efficiency at intermediate heteroplasmy values.