Mitochondrial Biogenesis in Neurons: How and Where

Round 1

Reviewer 1 Report

Mitochondrial biogenesis in neurons: how and where by Cardanho-Ramos and Morais comprehensively address the important issue of how mitochondrial biogenesis may occur ( especially in neurons that may have long axons) where nuclear encoded machinery required for mitochondrial biogenesis may  be far removed and not readily available at the periphery. They describe different scenarios that may occur in different neuron types and also within different locations in same cell. This is an important contribution to the field. I recommend it be accepted for publication after a few grammatical corrections for clarity.

Author Response

We would like to thank the reviewer for their kind words and time spent in assessing our work.

Reviewer 2 Report

The manuscript “Mitochondrial biogenesis in neurons: how and where” by Cardanho-Ramos & Morais reviews the mechanisms that promote mitochondrial biogenesis in neurons as mitochondrial dysfunction is at the base of neurodegenerative diseases. The authors especially analyse where and how mitochondrial biogenesis is conducted concluding that these mechanisms may differ among different types of neurons and that multiple mechanisms can take place, even in the same, cell depending on mitochondria location. Besides, they hypothesize that local protein synthesis is responsible for supplying with all the machinery that is necessary for mitochondrial replication in the periphery, following a pathway where Ca²⁺ and mTORC1 act as main regulators.

The review was well conducted and the results are clearly presented and English language and style are also fine. The conclusions are supported by bibliography but I have detected some spelling mistakes:

• Page 1, line 28: “Mitochondria are a two-membrane organelle….” should be “Mitochondria are two-membrane organelles….”
• Page 3, line 122: “AMPK as also been….” should be “AMPK has also been….”
• Page 4, line 150: “Notably it seems deacetylation….” should be “Notably it seems that deacetylation…”
• Page 4, line 155: “super oxide” should be “superoxide”
• NAD+/NADH in several points of text and figures should be NAD⁺/NADH

Author Response

We would like to thank the reviewer for their kind words and time spent in assessing our work.

We thank the reviewer for having highlighted these spelling mistakes, and we apologize for this. We have corrected all the mistakes in the revised manuscript (in Track Change mode).