Oligomerization of Selective Autophagy Receptors for the Targeting and Degradation of Protein Aggregates

Round 1

Reviewer 1 Report

In their manuscript, Chen and colleagues review the current knowledge regarding the mechanism of selective autophagy for the degradation of aggregates. Their literature review focuses on the oligomerisation of selective autophagy receptors. The manuscript is well written and would be of interest to scientists in the field of selective autophagy.

Some minor comments remain.

 

1. The manuscript focuses on receptor oligomerisation. This could be more explicit in the title of the manuscript for increased visibility.
2. The oligomerisation of receptors can be stress-specific. For example, oxidation of p62 upon oxidative stress allows for its oligomerisation (Carroll B et al., Nature Communications volume 9, Article number: 256 (2018)).
3. Unless the authors wish to focus on mammalian and yeast selective autophagy receptors, it might be worth citing some work showing that AtNBR1 also can oligomerise (Svenning et al. Autophagy 7:9, 993-1010; September 2011).
4. Line 4: the sentence should be “When and how is the selective targeting of protein aggregates conducted by autophagy receptors?”
5. P62 is interchangeably named SQSTM1 in the text. The authors should choose one or the other nomenclature or write p62/SQSTM1.
6. Figure 1: the figure may seem a little too simplistic. As the review focuses on selective autophagy and the implication of selective autophagy receptors for the targeting of cargo to the autophagosome, this should be highlighted in this figure.
7. Line 161: title of the new section is italicised while other titles are in bold font.
8. Many repeats may be superfluous. For example, sentences like “Autophagy was first thought to be a bulk degradation pathway, ...” are redundant (lines 61-63, 72, 162-163).
9. Figure 2: the figure legend could be expanded. Essential domains are shown on the proteins; I understand that similar domains have the same colour (AIM and LIR, Ub-binding domains). This could be explained in the legend.
10. Lines 183, 228: the letter “k” in NF-kB should be the character for the Greek letter “kappa”.
11. Lines 209-210: reference missing about the OPTN-mediated clearance of Salmonella.
12. Line 304-311: reference(s) missing.
13. Line 406: “PB1” instead of “BP1”.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

General comment

The review of Chen et al is a review that considers the molecular mechanisms and the roles of autophagy receptor proteins in selective autophagy for protein aggregates. This review gives the reader some important insight including new topics in autophagy field. Some minor revisions are desirable before publication, as commented below.

 

Comments

1. Line 81; the authors should add the reference published by Nakagawa et al. (doi: 10.1126/science.1103966).
2. Line 83; the authors should add the reference published by Singh et al. (doi: 10.1126/science.1129577).
3. This reviewer recommends the change “Isolated membrane” to “Isolation membrane” described on Line 112.
4. This reviewer recommends the change “the phagophore assembly site (PAS)” to “the phagophore assembly site (PAS), also known as preautophagosomal structure” described on Line 119.
5. Line 127; The authors should mention about the role of Atg9 as a lipid scramblase on isolation membrane, referring to a recent paper by Matoba et al. (doi: 10.1038/s41594-020-00518-w).
6. Line 132; Please describe more detail description here, as such Atg12-Atg5 • Atg16 and Atg8-phosphatidylethanolamine (PE), contribute to expansion and closure of phagophore/isolation membrane.
7. In Figure 1, the authors should illustrate the bridge between LC3/GABARAP family members and ubiquitinated substrates, according to description on Line 241.
8. Line 295; Please add the reference #68.
9. Line 401; Could you mention about sequestration mechanism according to wetting effect, referring to recent publication by Agudo-Canalejo et al.(doi: 10.1038/s41586-020-2992-3.).

 

Author Response

Please see the attachment.

Author Response File: Author Response.pdf