On 2014 Jan 18, Alexander I. Alexandrov commented:

In my opinion the authors slightly mislead the readers by the title and abstract of the paper. The work demonstrates that in the presence of the prion [RNQ1+], Rnq1 overexpression (in the form a fusion with RFP) results in cell growth defects and oxidative stress. The only key role of Hsp104 in this process is that it is required for the maintenance of the prion form of Rnq1, which is a well established fact. In my opinion the paper would be better named “Rnq1-RFP expression causes prion-mediated oxidative stress in yeast” or something of the sort. Also, the abstract states: “Expression of RNQ1-RFP in Saccharomyces cerevisiae cells led to the generation of the prion form of the protein and increased oxidative stress”. This is also misleading, since the prion form of Rnq1 was probably present in the parental strain before introduction of the fusion protein. It would be better to say that Rnq1-RFP joined pre-existing amyloids of wtRnq1. Notably, the article does not explicitly state that the parental strain was [RNQ1+]. In my opinion, the article lacks a very simple, yet informative experiment, where cells exhibiting oxidative stress could be cured of the prion by GuHCl and then assayed for alleviated growth defects and oxidative stress. This would provide more clear proof that the reduced toxicity and oxidative stress were caused by the prion and not by the deletion of HSP104. In the same vein, it would be interesting to compare cells with and without the [RNQ1+] prion (without any overexpression of Rnq1-RFP) in terms of their oxidative stress. Also, I was surprised to find no reference to papers which were the first to observe the toxic effects of Rnq1 overexpression and to identify the mechanism through which they were realized– PMID’s 18480252 and 22529103. The second article has a mechanistic explanation of the toxic effect and it would be interesting to see if the effects observed in this article are caused by the same mechanism. Notwithstanding these points, I think that the article is interesting and informative.

On 2014 Jan 17, Alexander I. Alexandrov commented:

None

On 2014 Jan 17, Alexander I. Alexandrov commented:

None

On 2014 Jan 18, Alexander I. Alexandrov commented:

In my opinion the authors slightly mislead the readers by the title and abstract of the paper. The work demonstrates that in the presence of the prion [RNQ1+], Rnq1 overexpression (in the form a fusion with RFP) results in cell growth defects and oxidative stress. The only key role of Hsp104 in this process is that it is required for the maintenance of the prion form of Rnq1, which is a well established fact. In my opinion the paper would be better named “Rnq1-RFP expression causes prion-mediated oxidative stress in yeast” or something of the sort. Also, the abstract states: “Expression of RNQ1-RFP in Saccharomyces cerevisiae cells led to the generation of the prion form of the protein and increased oxidative stress”. This is also misleading, since the prion form of Rnq1 was probably present in the parental strain before introduction of the fusion protein. It would be better to say that Rnq1-RFP joined pre-existing amyloids of wtRnq1. Notably, the article does not explicitly state that the parental strain was [RNQ1+]. In my opinion, the article lacks a very simple, yet informative experiment, where cells exhibiting oxidative stress could be cured of the prion by GuHCl and then assayed for alleviated growth defects and oxidative stress. This would provide more clear proof that the reduced toxicity and oxidative stress were caused by the prion and not by the deletion of HSP104. In the same vein, it would be interesting to compare cells with and without the [RNQ1+] prion (without any overexpression of Rnq1-RFP) in terms of their oxidative stress. Also, I was surprised to find no reference to papers which were the first to observe the toxic effects of Rnq1 overexpression and to identify the mechanism through which they were realized– PMID’s 18480252 and 22529103. The second article has a mechanistic explanation of the toxic effect and it would be interesting to see if the effects observed in this article are caused by the same mechanism. Notwithstanding these points, I think that the article is interesting and informative.