Figure 3.

A mathematical model for mitophagy. (A) Live imaging of GFP-ATG13 (green) translocations on a targeted mitochondrion (red) showing sequential translocations. Each frame is 0.8” and the entire sequence is shown. This wide-field imaging was not used for the quantitations but provided a more continuous view of the translocations. (B) Three representatives of regularized quantified time courses up to 400 s (i–iii). These plots are derived from spinning disk confocal images. (C) ATG13 mean time course (black line) after data synchronization, filtering, and regularization. The mean is shown with the confidence interval of the mean at 95% confidence level (magenta bars) and 1 standard deviation (black bars). (D) The delays of the upper and lower aggregation peaks, indicating how these increased over time exponentially. Mean and standard deviation of the time differences between upper and lower peaks are reported as annotations. These statistics define the model parameter t. (E) Model diagram for mitophagy events. This model extends the diagram in Figure 1B by including LC3 and the events for regulating the delays between aggregations. The concentration of LC3 was calculated before the event starting ATG13 accumulation was triggered. Therefore, LC3 inhibits ATG13 accumulation after a delay (Tau). (F) Model fitting for ATG13 kinetic rate constants using the 1st aggregation data set. The experimental data and model simulation are represented with red circles and a black line, respectively. (G) MT diameter density (I) and QQ plot (ii) against a normal distribution. 17 mitochondrial diameters were measured and analyzed. The reported mitochondria diameter mean and standard deviation define the model parameter MT_diam. (H) Model fitting for ATG13 (i) and the delay between aggregations (ii) using the data sets in panel C. The parameters t and MT_diam were fixed to their mean value during this stage of parameter estimation