When URLanelles are degraded by autophagy , typically some, but not all, of each URLanelle type are degraded. Autophagy selectivity must not only select the correct type URLanelle, but  must discriminate between URLanelles of the same kind . In the context of peroxisomes, we use computational models to explore the hypothesis that physical clustering of autophagy receptor proteins on the surface of URLanelle provides an appropriate all-or-none signal for degradation. The pexophagy receptor proteins NBR1 and p62 are well characterized, though only NBR1 is essential for pexophagy (Deosaran%DIFDELCMD < {\em %%% et al. , 2013). Extending earlier work by addressing the initial nucleation of NBR1 clusters on individual peroxisomes, we find that larger peroxisomes nucleate NBR1 clusters first and lose them due to competitive coarseninglast, resulting in significant size-selectivity favouring large peroxisomes. This effect can explain the increased catalase signal that results from experimental siRNA inhibition of p62. We also consider receptor cluster formation on individual peroxisomes with enhanced levels of ubiquitinand find that size-selectivity, but not cluster formation , is suppressed. Thus, our selectivity mechanism does not hinder selection of individual URLanelles via enhanced ubiquitination. NBR1 cluster formation provides a viable physical mechanism for all-or-none substrate selectivity in pexophagy .
Selective autophagy must not only select the correct type URLanelle, but also must discriminate between URLanelles of the same kind so that some but not all of URLanelles are removed. We propose that physical clustering of autophagy receptor proteins on URLanelle surface can provide an appropriate all-or-none signal URLanelle degradation. We explore this proposal using a computational model restricted to peroxisomes and the relatively well characterized pexophagy receptor proteins NBR1 and p62 %DIFDELCMD < {\em %%% . 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 URLanelles, suppresses size-selectivity but not cluster formation . Our proposed selectivity mechanism thus allows all URLanelles to be degraded, while otherwise selecting only a portion URLanelles for degradation .
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