The Intracellular Distribution of the Small GTPase Rho5 and Its Dimeric Guanidine Nucleotide Exchange Factor Dck1/Lmo1 Determine Their Function in Oxidative Stress Response
Round 1
Reviewer 1 Report
1st July, 2022
Review of the Manuscript ID: ijms-1802728, by L. Bischof et al., entitled: “The Intracellular Distribution of the Small GTPase Rho5 and its Dimeric Guanidine Nucleotide Exchange Factor Dck1/Lmo1 Determine Their Function in Oxidative Stress Response” that is intended to be published as the Article in International Journal of Molecular Sciences
(separate Microsoft Word file as Reviewer Attachment for Manuscript ID ijms-1802728 Int. J. Mol. Sci. 1st July 2022 that includes Comments to the Authors is also uploaded)
Considering research highlight, contribution of the Authors to the progress in the research area, thorough manner of data presentation, very well writing in English, abundance of Materials and Methods, Results as well as diligent tabular and graphic/photographic documentation, the quality of this paper deserves praise and merits my support. The Authors have received the high scores from me for the originality, importance of the work and the scientific value of their paper. In my opinion, the current paper provides insightful interpretation of topical and coming trends in the subfields of molecular biology focused on comprehensive research aimed to precisely ascertain the importance of Rho-type GTPases and their dimeric guanidine nucleotide exchange factors Dck1/Lmo1 for various scenarios of molecular pathways related to the cellular response and resilience to oxidative stress triggered by oxygen-derived free radicals and related oxidants. Cumulatively, taking all these facts into account, I strongly recommend the Editorial Board to allow for publication of this valuable paper in International Journal of Molecular Sciences, after the minor revision of the manuscript will have been completed by the Authors and provided that the Authors are ready to consider all the Reviewer comments indicated below:
1) There is a lack of the separate Conclusions section in the paper. For that reason, this section should have been added at the end of the manuscript to comprehensively summarize the manuscript and include important paragraphs focused on research highlight and future goals.
2) There is a lack of the separate Abbreviations section in the paper. For that reason, this section should have been added to thoroughly elucidate and expand a wide range of the in-text abbreviations, which have been used by the Authors in all the subsections of their paper.
3) The References section has to be prepared in the format compatible with the requirements of International Journal of Molecular Sciences.
General Comment of the Reviewer:
Before the manuscript will have been accepted for publication in International Journal of Molecular Sciences, it requires the minor revision (according to all the remarks and suggestions of the Reviewer).
Author Response
Considering research highlight, contribution of the Authors to the progress in the research area, thorough manner of data presentation, very well writing in English, abundance of Materials and Methods, Results as well as diligent tabular and graphic/photographic documentation, the quality of this paper deserves praise and merits my support. The Authors have received the high scores from me for the originality, importance of the work and the scientific value of their paper. In my opinion, the current paper provides insightful interpretation of topical and coming trends in the subfields of molecular biology focused on comprehensive research aimed to precisely ascertain the importance of Rho-type GTPases and their dimeric guanidine nucleotide exchange factors Dck1/Lmo1 for various scenarios of molecular pathways related to the cellular response and resilience to oxidative stress triggered by oxygen-derived free radicals and related oxidants. Cumulatively, taking all these facts into account, I strongly recommend the Editorial Board to allow for publication of this valuable paper in International Journal of Molecular Sciences, after the minor revision of the manuscript will have been completed by the Authors and provided that the Authors are ready to consider all the Reviewer comments indicated below:
We thank the reviewer for his/her time and effort and for the really enthusiatic comments. We have taken into account the suggestions and corrected the manuscript as outlined, below (responses highlighted in bold).
1) There is a lack of the separate Conclusions section in the paper. For that reason, this section should have been added at the end of the manuscript to comprehensively summarize the manuscript and include important paragraphs focused on research highlight and future goals.
The conclusion section has now been separated in a new section after the discussion.
2) There is a lack of the separate Abbreviations section in the paper. For that reason, this section should have been added to thoroughly elucidate and expand a wide range of the in-text abbreviations, which have been used by the Authors in all the subsections of their paper.
A list of abbreviations has been added after the Materials and Methods section.
3) The References section has to be prepared in the format compatible with the requirements of International Journal of Molecular Sciences.
Thank you for the comment and sorry for the oversight. The reference list has been revised according to the requirements of IJMS.
Reviewer 2 Report
Dear Editor, thank you for the opportunity to review this exciting manuscript, dealing with essential findings entitled “The Intracellular Distribution of the Small GTPase Rho5 and 2 it's Dimeric Guanidine Nucleotide Exchange Factor Dck1/Lmo1 3 Determine Their Function in Oxidative Stress Response”. All findings are interesting, and the article includes a balanced and critical view of the findings. However, similar findings and approaches are already published in the article The small GTPase KlRho5 responds to oxidative stress and affects cytokinesis”. I would like to know the novelty of this article, compared to the stated published article.
Author Response
I would like to know the novelty of this article, compared to the stated published article.
We thank the reviewer for the critical reading of the manuscript and the praise of the findings and layout. As for the new findings in comparison to the work cited on KlRho5, we would like to clarify this by three points:
- The work cited deals with the Rho5 and GEF homologues in the milk yeast K. lactis, rather than with the proteins of S. cerevisiae, described in the current manuscript. There are several important differences between the two yeast, which merits the previous work, but also makes clear that the physiological roles have to be assessed in the proper yeast, and that there is no overlap in results.
- In the work on KlRho5 we found that the GTPase and the subunits of its dimeric GEF translocate rapidly to mitochondria under stress, as do their S. cerevisiae counterparts. However, we did not check the behaviour of the GEF subunits in deletion mutants, i.e. independent from each other, which is a key point of the current investigation in S. cerevisiae. In fact, the new findings led us to propose a different model to our previous views (outlined in Fig. 1), in that it is not the trimeric complex Rho5/Dck1/Lmo1 that translocates in unison to the mitochondria, but that rather the GEF may be recruited first, followed by the GTPase.
- Another key feature of the current manuscript, as opposed to the work on KlRho5, is the attachment of Rho5 and the GEF subunits to either the plasma or the mitochondrial outer membrane, and its physiological consequences. These have not been addressed, previously.
