Sub-Cellular Metabolomics Contributes Mitochondria-Specific Metabolic Insights to a Mouse Model of Leigh Syndrome
Round 1
Reviewer 1 Report
In this manuscript authors tried to establish the underlying metabolite responsible for complex I deficiency disease. They got the insight about the different metabolite behavior when used Ndufs4 ko mouse brain and skeletal muscle. They performed untargeted 1H NMR and semi-targeted LC-MS/MS from mitochondrial and cytosolic fractions. I found they have very targeted approach in this experiments. Their all data analysis is done very thorough and careful way and based on their data their interpretation is very much co-related. They observed many specific changes in compartmental specific metabolites, though in terms of perfect pathway specific analysis is missing but found many metabolites that falling in different pathway. Overall this manuscript deserved publication in this Journal in current form.
Author Response
Thank you for your rapid review and kind response. Please find attached our revised manuscript
Reviewer 2 Report
In this manuscript, the authors performed 1H-NMR and LC-MS/MS metabolomics on the purified brain and quadriceps muscle mitochondria and cytosol from male Ndufs4 KO mice (n = 8), as well as age- and sex-matched controls (n = 8). A specific set of metabolites were identified in each compartment thus supporting this technical approach. In my opinion, the experiments are well-performed and support the authors' conclusions. The paper is also well written. I have only a minor comment. I suggest including a figure, a graphical abstract of the work, that summarizes the observed metabolic alterations and that underlies the possible metabolic crosstalk between muscle and brain.
Author Response
Thank you for your rapid review and kind response. Please find attached our revised manuscript.
We prepared a graphical abstract like you suggested. Since our manuscript already contains 6 figures and 1 table, we did not add the graphical abstract to the actual manuscript, but left it to be published as a graphical abstract online. If you however feel that we should include the graphical abstract as an additional figure in the manuscript, we are more than willing to do this
Author Response File: 
Author Response.pdf
