PONE-D-19-21805

Evolutionarily conserved susceptibility of the mitochondrial respiratory chain to SDHI pesticides and its consequence on the impact of SDHIs on human cultured cells

PLOS ONE

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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: Yes

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Reviewer #1: This manuscript describes the effects of several Succinate dehydrogenase inhibitors (SDHIs) on different organisms (Botrytis cinerea, Homo sapiens, Lumbricus sp. and Apis mellifera) and on cell samples derived from healthy individuals as well as cells derived from SDH-deficient, Friedreich's ataxia and Alzheimer patients. The manuscript is generally well-written and presents some interesting results that will be of interest to the field. Of particular interest: the masking effect of glucose when testing the effects of SDHIs and the possible effects of the inhibitors on the environment and non-target organisms.

However, there are some aspects of the study presentation that would make these findings more accessible. Notably:

Material and Methods:

- Human cultured fibroblasts and HEK cells -

The two types of media are described at the beginning of this paragraph but are not named immediately. The two names GlucoMax and MitoMax are shown only at the end of the paragraph. This is a bit confusing.

Results section:

- Effects of SDHIs on the mitochondrial respiratory chain -

It would help to report the SDHIs concentrations used in agriculture as a comparison for the IC50 results.

- SDHIs and the viability of cultured human cells -

Half life of SDHIs? The experiments last for 12/14 days without the medium getting changed. The differences seen between the compounds could be due to differences in their respective half lives.

Fig. 4, B: only the graph for bixafen in permissive medium is reported. Could you show the fluxapyroxad graph in permissive medium as well?

Minor corrections:

L206/207: this sentence is a bit confusing. Try rephrasing.

L253: the IC50 is reported only for bixafen and not for isopyrazam. Both of them are discussed in this sentence, therefore I would include both IC50 values.

L256: the IC50 reported for bixafen on CIII is 15.3 µM, the table says 15.5 µM

L290: add "C" inside the brackets (Fig 3A, B and C) not (Fig 3A, B)

L321 to 324: this sentence is not very clear. Try rephrasing.

L329: the "D" needs to be bold.

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Reviewer #1: No

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Evolutionarily conserved susceptibility of the mitochondrial respiratory chain to SDHI pesticides and its consequence on the impact of SDHIs on human cultured cells

PONE-D-19-21805R1

Dear Dr. Rustin,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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With kind regards,

Annalisa Pastore

Academic Editor

PLOS ONE

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