Calcium Overload and Mitochondrial Metabolism

Round 1

Reviewer 1 Report

Summary: In this article, Walkon et al. provide a review of the literature relating to calcium overload and its role in mitochondrial metabolism. This article is interesting but has many concerns, and the following points should be considered before publication.

 Major concerns:

1. This review focuses on a topic of current interest but does not add any novel information; many key findings are missing. It is mentioned that calcium modulates mitochondrial metabolism, but the mechanism of this modulation is not discussed.
2. Some of the citations are irrelevant and do not cover recent studies or do not match the text. For example, the relevance of Ref.3 in the introduction (Line no. 35) is unclear. In addition, there is no reference for mentioned major organelles other than the liver (Line No. 82).
3. For calcium homeostasis, entry, and exit pathways, authors have mentioned only MCU and NCLX; other components of mitochondrial calcium uniporter are not mentioned.
4. There are no legends for Figure 3. it is just copied directly from Figure 2.
5. There is no discussion about the disease perspective concerning calcium overload and mitochondrial metabolism.
6. In conclusion, the authors mentioned “several open questions” It would be interesting to add the hypothesis-driven answer to these questions and future directions and provide their perspectives.
7. This article is not proofed, and there are many semantic errors.

Author Response

Author Response File: Author Response.pdf

Reviewer 2 Report

-Figure 3 has the wrong caption (copied from figure 2). Please provide for the uninitiated reader a clear explanation of what the curves, arrows and shaded areas in the figure denote.

-It would be good to provide references to original articles in the captions of figures showing experimental data.

Author Response

Author Response File: Author Response.pdf