Reactive Oxygen Species Signaling Pathways: Arbiters of Evolutionary Conflict?
Round 1
Reviewer 1 Report
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Reviewer 2 Report
In this review, Blackstone presents reactive oxygen species as arbiters of evolutionary conflicts associated with the rise of cooperation between organisms. Overall, the manuscript is very-well written, ideas are logically presented and evidence to support the statements/conclusions is given. On interesting secondary point is the consideration ROS having a signaling role, instead of simply causing cell death in coral bleaching; a view which is not commonly acknowledged. I think this manuscript would be of broader impact if the author considered to add some concepts directly related to the topics addressed therein that seem to have been ignored:
1. The differentiation between of oxidative distress and eustress, concepts and terms recently defined by Helmut Sies (978-0128186060; 10.1016/j.redox.2021.101867), would make the distinction between situations in which ROS signaling is “under control” and ROS signaling is “out of control” damaging biomolecules and triggering cell death.
2. Since the author goes back to very early in the history of life (back to the LUCA), I think it is worth mentioning the role of reactive sulfur species in early evolution and their relation with the rise of ROS management antioxidant systems (see: 10.1016/j.freeradbiomed.2019.01.020; 10.1016/j.cbpa.2020.110824)
3. Lastly, considering the discussion on interplay between bioenergetics and redox balance (or ROS levels), I think it is worth considering another point of contact between these two, which is the supply of reducing equivalents to antioxidant systems by NADPH. Steady state levels of ROS at a given time and location depend not only on their production but also their neutralization by antioxidant systems. Glutathione-dependent and thioredoxin-dependent systems, major antioxidant systems (or redox hubs), are highly dependent on the availability of NADPH (10.1089/ars.2012.4599). For example, human skin cells redirect glucose flux to NADPH-generating pathways in response to oxidative challenges within minutes (10.1016/j.molcel.2015.06.017). In D. melanogaster, the overexpression of G6PD increases levels of NADPH and enhances resistance to oxidative challenges (10.1074/jbc.M805832200). Mice with impaired NADPH production suffer more oxidative damage to DNA in the brain than those with normal capacity (10.1021/cn400079y). See also: 10.1038/ncomms10894.
Author Response
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Round 2
Reviewer 1 Report
The author has addressed my concerns
