FIS7 loss drives mitochondrial elongation and synaptic decline in aging cortical neurons
L. Okafor, M. Brandt, S. Iyer, J. Whitcombe
- Revision risk
- 72/100 · High
- Major
- 4
- Minor
- 3
- References flagged
- 4of 42
Summary
A clear, well-motivated study whose central claim currently outruns its evidence. Referees are likely to ask for a rescue experiment, a culture-level reanalysis of the spine data, and either in vivo aging data or a narrower title.
Major concerns
01 · major · Causal claim · Results · Fig. 3
The causal claim rests on a single shRNA with no rescue
“demonstrating that FIS7 is required for the maintenance of dendritic spines in mature neurons.”
Why a reviewer will raise itEvery loss-of-function result in Fig. 3 uses one shRNA. Reviewers routinely ask whether the phenotype is off-target, and “required” is stronger than knockdown alone can support.
What to changeRe-express an shRNA-resistant FIS7 and show spine density recovers, or repeat the key panels with a second, independent shRNA or a CRISPR knockout. Until then, soften “required” to “contributes to”.
02 · major · Statistics · Methods · Fig. 2D
Neurons, not animals, are treated as independent replicates
“n = 142 neurons from 3 cultures; p < 0.001, two-tailed t-test.”
Why a reviewer will raise itNeurons from the same culture are not independent. Pooling them inflates n and can turn a culture-level effect into an apparently strong one — a frequent reason for a major-revision request.
What to changeReport one value per culture (or per animal) and test on those, or fit a mixed-effects model with culture as a random effect. State the biological n in every legend.
03 · major · Novelty · Introduction · ¶4
The novelty claim overlooks the Drp1 literature
“This is the first report linking mitochondrial morphology to synaptic decline.”
Why a reviewer will raise itLinks between fission machinery and synapse loss are well established for Drp1. A reviewer in this field will name those papers and question what is new here.
What to changeCite the Drp1 work directly and state the specific advance — an FIS7-dependent, age-restricted mechanism — rather than a first-ever link.
04 · major · Missing experiment · Results · Fig. 4–5
Aging is claimed in the title but tested only in culture
“Together, these data establish FIS7 as a driver of synaptic decline during aging.”
Why a reviewer will raise itAll aging data come from neurons kept 21 days in vitro. Reviewers will ask for at least one in vivo time point before accepting an aging claim.
What to changeAdd FIS7 levels and spine counts from young and aged mouse cortex, or narrow the title and abstract to in-vitro maturation.
Minor concerns
05 · minor · Key information · Fig. 4 legend
Animal age and sex are missing from the Fig. 4 legend
“Cortical tissue was collected and processed as described.”
Why a reviewer will raise itMost life-science journals require age and sex for every animal experiment; editors return manuscripts for this at triage.
What to changeAdd age (in weeks) and sex for each group to the legend and the Methods.
06 · minor · Figures · Fig. 1B
Scale bars are absent from the confocal panels
“Representative images of MitoTracker-labelled neurons.”
Why a reviewer will raise itWithout scale bars, mitochondrial length cannot be judged from the images, which is the central measurement of the figure.
What to changeAdd a scale bar to every micrograph and give its length in the legend.
07 · minor · Statistics · Fig. 3C
Western blot normalisation is not described
“FIS7 protein was reduced by 68% relative to control.”
Why a reviewer will raise itReviewers will ask which loading control was used and whether bands were within the linear range.
What to changeName the loading control, show full blots in a supplement, and describe the quantification.
Reference check
42 references looked up in Crossref and Retraction Watch: 38 verified, 1 retracted, 2 DOI mismatch, 1 not found. Flagged entries first.
| [12] | Zhang H.-L. et al. Cell Rep 18, 1102–1115 (2017)doi:10.5555/celrep.2017.1102 | Retracted | Retraction notice issued; check whether the claim it supports still stands. |
| [19] | Kowalski T. & Reyes A. J Neurosci 40, 512–527 (2020)doi:10.5555/jneuro.2020.0512 | DOI mismatch | DOI points to a different paper by other authors. |
| [31] | Moreau P. Mitochondrion 58, 44–51 (2021)No DOI | Not found | No record in Crossref under this title, journal or year. |
| [7] | Adeyemi K. et al. J Cell Sci 132, jcs2281 (2019)doi:10.5555/jcs.2019.2281 | Verified | DOI resolves to the cited article. |
| [23] | Hallström R. et al. Neuron 102, 81–96 (2019)doi:10.5555/neuron.2019.0081 | Verified | DOI resolves to the cited article. |