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ATG13 dynamics in non-selective autophagy and mitophagy: insights from live imaging studies and mathematical modelling

View ORCID ProfilePiero Dalle Pezze, Eleftherios Karanasios, Varvara Kandia, Maria Manifava, Simon A. Walker, View ORCID ProfileNicolas Gambardella Le Novère, View ORCID ProfileNicholas T. Ktistakis
doi: https://doi.org/10.1101/370114
Piero Dalle Pezze
The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK
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Eleftherios Karanasios
The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK
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Varvara Kandia
The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK
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Maria Manifava
The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK
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Simon A. Walker
The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK
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Nicolas Gambardella Le Novère
The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK
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  • ORCID record for Nicolas Gambardella Le Novère
Nicholas T. Ktistakis
The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK
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  • ORCID record for Nicholas T. Ktistakis
  • For correspondence: nicholas.ktistakis@babraham.ac.uk
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Abstract

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.

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  • Following submission to a journal and rejection, the paper has been edited throughout. The structure of the manuscript and its message remain the same. One figure has been removed from the main text.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 10, 2019.
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ATG13 dynamics in non-selective autophagy and mitophagy: insights from live imaging studies and mathematical modelling
Piero Dalle Pezze, Eleftherios Karanasios, Varvara Kandia, Maria Manifava, Simon A. Walker, Nicolas Gambardella Le Novère, Nicholas T. Ktistakis
bioRxiv 370114; doi: https://doi.org/10.1101/370114
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ATG13 dynamics in non-selective autophagy and mitophagy: insights from live imaging studies and mathematical modelling
Piero Dalle Pezze, Eleftherios Karanasios, Varvara Kandia, Maria Manifava, Simon A. Walker, Nicolas Gambardella Le Novère, Nicholas T. Ktistakis
bioRxiv 370114; doi: https://doi.org/10.1101/370114

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