The Passage of H₂O₂ from Chloroplasts to Their Associated Nucleus during Retrograde Signalling: Reflections on the Role of the Nuclear Envelope

Round 1

Reviewer 1 Report

In this manuscript authors try to unravel the route of hydrogen peroxide from chloroplast to nucleus during retrograde signalling. Since H₂O₂ is produced also by other subcellular compartments they focus on the connection between the two organelles that might be the key for the H₂O₂-mediated signal specificity. Authors analyse different types of connection, particularly reporting about the putative/relevant role of endoplasmic reticulum (ER). They propose models based on information available from other eukaryotic cells being aware that this could be a merely speculation that needs experimental validation.  

I found the paper very interesting and stimulating for further investigations.

Authors refer to the most relevant literature however I suggest revising this section (see ref 60 and merge refs 92 and 93).

Author Response

We thank the revieer for their kind comments. The two mistakes in the referecne swection (refs 92-93 merged and Ref 61) corrected now. In adition, we found a few further typographical errors in teh reference section which we have corrected.

Reviewer 2 Report

In this manuscript, the authors review the passage of H₂O₂ from chloroplasts to their associated nucleus during retrograde signalling: Reflections on the role of the nuclear envelope.

Hydrogen peroxide (H₂O₂), generated during photosynthesis, is proposed to both initiate and transduce a retrograde signal in response to photoinhibitory light intensities. Signalling specificity achieved by chloroplast-sourced H₂O₂ for signal transduction may be dependent upon the oft-observed close association of a proportion of these organelles with the nucleus. In this review, we consider more precisely the nature of the close association between a chloroplast appressed to the nucleus and the requirement for H₂O₂ to cross both the double membranes of the chloroplast and nuclear envelopes. Of particular relevance is that the endoplasmic reticulum (ER) has close physical contact with chloroplast and is contiguous with the nuclear envelope. Therefore, the perinuclear space, which transducing H₂O₂ molecules would have to cross, may have an oxidising environment similar to the ER lumen. Furthermore, based on studies in animal cells, the ER lumen may be a significant source of H₂O₂ in plant cells arising from the oxidative folding of proteins. If this is the case, then there is potential for the ER lumen/perinuclear space to be an essential location to modify chloroplast-to-nucleus H₂O₂ signal transduction and thereby introduce modulation by adding different environmental cues. These would include, for example, heat stress and pathogen infection, which induce the unfolded protein response characterized by an increased H₂O₂ level in the ER lumen.

The manuscript is written very well scientifically and tick all the boxes—congratulation to the authors. I could not find any major fault in this manuscript

The manuscript can be accepted after minor changes.

At L155 and has the effect of bring the proline-rich to and has the effect of bringing the proline-rich.

L184 to the nucleus then it to to the nucleus, then it.

Author Response

We thank the reviewer for their kind words regrding our manuscript. The two minor grammatical errors mentioned have been corrected.