Dynamic modelling suggests differential mechanisms for initiation of non-selective autophagy and mitophagy
During autophagy, the ULK complex nucleates autophagic precursors which give rise to autophagosomes. We analysed by live imaging and mathematical modelling translocation of ATG13 (part of ULK complex) to autophagic puncta in starvation-induced autophagy and ivermectin-induced mitophagy. In non-selective autophagy, the intensity and duration of ATG13 translocation approximated a normal distribution whereas wortmannin reduced this and shifted to a log-normal distribution. During mitophagy, multiple translocations of ATG13, with increasing time between peaks were observed. We hypothesised that these multiple translocations arise because engulfment of mitochondrial fragments requires successive nucleations of multiple phagophores on the same target, and a mathematical model based on this idea reproduced the oscillatory behaviour. Significantly, model and experimental data were also in agreement that the number of ATG13 translocations is directly proportional to the diameter of the targeted mitochondrial fragments. Our data provide novel insights into the early dynamics of selective and non-selective autophagy.