All reviews of published articles are made public. This includes manuscript files, peer review comments, author rebuttals and revised materials. Note: This was optional for articles submitted before 13 February 2023.
Peer reviewers are encouraged (but not required) to provide their names to the authors when submitting their peer review. If they agree to provide their name, then their personal profile page will reflect a public acknowledgment that they performed a review (even if the article is rejected). If the article is accepted, then reviewers who provided their name will be associated with the article itself.
All concerns of the reviewers were addressed, and revised manuscript is acceptable now.
[# PeerJ Staff Note - this decision was reviewed and approved by Gwyn Gould, a PeerJ Section Editor covering this Section #]
The authors responded point by point to my comments, making the corresponding changes. In addition, they included the comments of the other reviewer. I think that in its current state it could eventually be published.
.
.
well
well
well
Please address concerns of both reviewers and amend manuscript accordingly.
[# PeerJ Staff Note: Please ensure that all review and editorial comments are addressed in a response letter and any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate. #]
GENNERAL COMMENTS
The manuscript titled “Ferroptosis in ischemia reperfusion injury: A mini-review of the relationship between ferroptosis and mitophagy” by Liu et al., briefly describes the main pathways that could link ferroptosis and mitophagy at the intracellular level in the context of ischemia reperfusion injury. Ferroptosis is a hot topic in recent years and quite interesting from a therapeutic point of view due to the implications that modulating it could have in the different pathophysiological models of diseases The authors begin the review giving a general context of IRI, ferroptosis and mitophagy, to then describe the main mechanisms of ferroptosis, mention 3 pathways that would relate ferroptosis and mitophagy, together with some compounds that could modulate that and ending with a conclusion where it is deepened the mechanics of the authors' hypothesis. As for the literature and the state of the art, it lacks depth in some topics that I will mention in more specific comments, in addition to some errors in the structure.
A) The citations must be corrected, there are several references with the same last name of the first author and the same year, but there is no way to differentiate between them in order to review them. Example: Liu et al., 2021 could be any of these references:
1) Liu, L., Li, Y., & Chen, Q. 2021. The emerging role of FUNDC1-mediated mitophagy in cardiovascular diseases. Front Physiol 12: 807654 DOI 10.3389/fphys.2021.807654.
2) Liu, M. R., Zhu, W. T., & Pei, D. S. 2021. System Xc(-): a key regulatory target of ferroptosis in cancer. Invest New Drugs 39(4): 1123-1131 DOI 10.1007/s10637-021-01070-0.
3) Liu, X., Qi, K., Gong, Y., Long, X., Zhu, S., Lu, F., et al. 2021. Ferulic acid alleviates myocardial ischemia reperfusion injury via upregulating AMPKalpha2 expression-mediated ferroptosis depression. J Cardiovasc Pharmacol 79(4): 489-500 DOI 10.1097/FJC.0000000000001199.
4) Liu, X. J., Lv, Y. F., Cui, W. Z., Li, Y., Liu, Y., Xue, Y. T., et al. 2021. Icariin inhibits hypoxia/reoxygenation-induced ferroptosis of cardiomyocytes via regulation of the Nrf2/HO-1 634 signaling pathway. FEBS Open Bio 11(11): 2966-2976 DOI 10.1002/2211-5463.13276
5) Liu, Y., Wang, Y., Liu, J., Kang, R., & Tang, D. 2021. Interplay between MTOR and GPX4 signaling modulates autophagy-dependent ferroptotic cancer cell death. Cancer Gene Ther 28(1-2): 55-63 DOI 10.1038/s41417-020-0182-y
Same with Li et al., 2021:
1) Li, G., Li, J., Shao, R., Zhao, J., & Chen, M. 2021. FUNDC1: A promising mitophagy regulator 590 at the mitochondria-associated membrane for cardiovascular diseases. Front Cell Dev Biol 9: 591 788634 DOI 10.3389/fcell.2021.788634.
2) Li, N., Jiang, W., Wang, W., Xiong, R., Wu, X., & Geng, Q. 2021. Ferroptosis and its emerging 601 roles in cardiovascular diseases. Pharmacol Res 166: 105466 DOI 10.1016/j.phrs.2021.105466.
3) Li, S., Zhang, J., Liu, C., Wang, Q., Yan, J., Hui, L., et al. 2021. The role of mitophagy in 603 regulating cell death. Oxid Med Cell Longev 2021: 6617256 DOI 10.1155/2021/6617256.
Same with Wang et al., 2020 or Wang et al., 2021, so they should check to correct all references that could cause confusion.
B)Figure 3 lacks to show that the excess of mitophagy could ultimately lead to an increase in iron and thereby increase the fenton reaction and the damage at the cellular level as a result of the ROS that are formed.
C) Figure 2 has the components very close to each other at the bottom. I suggest rearranging it.
The methodology is suitable for a literary review
a) The iron overload section is a bit weak. What importance do you give to the Polyol pathway or myocardial hemorrhage in the increase in iron? It remains to be explained how iron is linked to the increase in ROS, specifically the fenton reaction and hydroxyl radical formation.
b) In the section on lipid peroxidation this should be contextualized to MIRI and ferroptosis.
c) It is missing to include more connection between mitochondria and ferroptosis (in addition to mitophagy) to be able to give the importance that mitochondria has in the context of ferroptosis.
d) I suggest deepening the hypothesis that links HIF with mitophagy, MIRI decrease and ferroptosis in its respective section and in the conclusion give the implications of this could have, instead of leaving all the bulk of the information for the conclusion.
e) Improve wording of the paragraph on the pathological process of the MIRI, specifically that of ischemia
The title should refer to injury due to cardiac ischemia reperfusion, since that is what they focus on in the development of the manuscript.
The authors aimed to systematically explore the relationship between ferroptosis and mitophagy in ischemia-reperfusion injury. It is an interesting in-depth review, but some points as specifically described below should be addressed before publication.
1. The authors finally summarized the potential drugs or compounds in the treatment of MIRI via the mechanism of regulating autophagy and ferroptosis, but in the abstract, the authors did not conclude the results or mentioned it, please added it to the abstract.
2. In the part of “Absorption and utilization of iron” (Line 155), the author should further summarize the process of iron metabolism in vivo from absorption to ferroptosis, which could make the point clearer.
3. We know that it is difficult to find natural compounds that are effective against MIRI. Some compounds may not be clinically effective even if they work in experiments. Research based on certain herbs known to treat MIRI might broaden the range of active ingredient screening. If possible, it is recommended to add some alternative or traditional medicine for MIRI treatment in Table 1.
4. In the part of “Conclusions and perspective”, it should be briefly highlighted the conclusion of the review and then emphasized the perspective of your findings. it should be divided into several points to make it clear for readers. For example, the relationship between mitophagy and ferroptosis, the involved mechanism or pathways, and the potential compounds, etc.
5. We recommend the authors of this review add more literature on ferroptosis published in 2022.
6. The part of “Absorption and utilization of iron” should be in front before the part of “MIRI and mitophagy”.
7. Iron overload, GPX4, system Xc- system, and lipid peroxidation is the classical pathway of ferroptosis. In addition, CoQ10/FSP1 axis and GCH1/BH4/DHFR axis also play an important role in regulating ferroptosis. Therefore, I suggest that it should be made clear that what is discussed here is the relationship between classical ferroptosis and mitophagy.
8. Should the authors further analyze the relationship between ferroptosis and mitophagy from the perspective of gene levels such as lncRNAs?
9. In figure 1, the font size of “Duodenum Cytochrome B” needs to be adjusted.
All text and materials provided via this peer-review history page are made available under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.