A Model of Autophagy Size Selectivity by Receptor Clustering on Peroxisomes

Frontiers in Physics

Brown, Aidan I.¹  Rutenberg, Andrew D.² 

[1] Department of Physics and Atmospheric Science, Dalhousie University, Halifax, NS, Canada;Department of Physics, Simon Fraser University, Burnaby, BC, Canada

关键词: pexophagy;    selective autophagy;    Peroxisomes;    nbr1;    p62;    receptor clustering;    Biological Physics;    Computational modelling;   

DOI  :  10.3389/fphy.2017.00014

学科分类：物理（综合）

来源: Frontiers

【 摘 要 】

Selective autophagy must not only select the correct type of organelle, but also must discriminate between individual organelles of the same kind so that some but not all of the organelles are removed. We propose that physical clustering of autophagy receptor proteins on the organelle surface can provide an appropriate all-or-none signal for organelle degradation. We explore this proposal using a computational model restricted to peroxisomes and the relatively well characterized pexophagy receptor proteins NBR1 and p62. We find that larger peroxisomes nucleate NBR1 clusters first and lose them last through competitive coarsening. This results in significant size-selectivity that favors large peroxisomes, and can explain the increased catalase signal that results from siRNA inhibition of p62. Excess ubiquitin, resulting from damaged organelles, suppresses size-selectivity but not cluster formation. Our proposed selectivity mechanism thus allows all damaged organelles to be degraded, while otherwise selecting only a portion of organelles for degradation.

【 授权许可】

CC BY