Cell Biology

Evaluation Summary:

This paper is of broad interest to researchers studying chromosome structure. Using a powerful reconstitution system, the authors dissect the function of the chromosome organising complex, condensin II. Several findings, if supported by some additional analyses, are surprising and thus have the potential to fuel further mechanistic studies of condensin function.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Evaluation Summary:

Kang et al. studied the role of cystathionine beta-synthase , an enzyme involved in homocysteine catabolism, in the senescent state imposed by oncogenic Akt. They find that this enzyme facilitates the acquisition of features of senescence, and is frequently silenced in tumors, whereas re-expressing it reduces cell proliferation. This manuscript is potentially of interest to cancer biologists, particularly those studying oncogene-induced senescence and mechanisms of senescence escape in cancers.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

The mechanisms that control cholesterol movement from the plasma membrane (PM) to the endoplasmic reticulum (ER) remain poorly understood. Here, Ogasawara and Ueda propose an intriguing mechanism whereby ABCA1, a membrane protein, moves cholesterol from the inner to the outer leaflet of the PM to keep the cholesterol away from intracellular Aster proteins that move cholesterol to the ER. When cholesterol builds up beyond a threshold, it accumulates on the inner leaflet and is transported to ER by Asters. If strengthened by the analysis of the endogenous ABCA1 and more physiological cholesterol manipulation, this work will be of significant interest to scientists studying lipid metabolism and transport.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Evaluation Summary:

This manuscript reports a striking finding, which should be of interest to cell biologists and biophysicists. The authors use an innovative approach to recruit clathrin to mitochondrial membranes and observe the budding and fission of clathrin-coated vesicles. The study leads to a much clearer view of how the clathrin lattice functions in endocytosis.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Overall this study confirms that TNF-α is increased in peripheral blood B cells from PCOS and metformin decreased production. The study demonstrates the potential mechanism for the increase in TNF-α and reduction due to metformin. This is demonstrated in humans as well as in a mouse model of PCOS. Overall this is a well designed study demonstrating the impact of Metformin on immune function in PCOS.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Evaluation Summary:

Catsburg et al. provide a new descriptive characterization of clathrin structures in spines vs dendrites using an excellent knock-in approach they recently developed. These results carefully validate earlier findings using the CRISPR approach and constitute useful baseline information, which would be useful in examining changes in the zone induced by neuronal activity or synaptic plasticity.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript.The reviewers remained anonymous to the authors.)

Evaluation Summary:

This paper bears on cardiac pro-arrhythmic findings reported on Duchenne Muscular Dystrophy. iPSC-CMs reprogrammed from cardiomyopathic DMD patients showed a dysfunctional NaV1.5-Kir2.1 channelosome relatable to reduced cardiac excitability and conduction. These findings suggests a possible clinical rescue of this phenotype by introducing the scaffolding protein α1-syntrophin.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Evaluation Summary:

Damaged chromatin displays an increase in nuclear mobility, but the importance of this response in homologous recombination (HR) repair is under debate. This study shows tight temporal coordination between HR repair events in budding yeast, where the increase in the mobility of repair sites follows resection and precedes chromosome pairing and gene conversion. With several elegant assays, the authors demonstrate that this temporal correlation remains intact in conditions that either delay resection or promote resection. This is consistent with the role of increased mobility in promoting chromosome pairing and HR progression, downstream from resection.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Evaluation Summary:

In this paper, the authors study distal tuft cells that are induced by influenza and bleomycinthe and find that Tuft cells originate from p63+ distal cells in virally-induced dysplastic regions of the lung as evidenced by lineage tracing. Interestingly, single cell sequencing reveals heterogeneity of tuft cells reminiscence of the murine tracheal tuft cells and supports a p63+ cell origin. They also found that the tuft cell induction is independent of the IL-25 and IL-4Ra pathway and since type 2 inflammation has been associated with tuft cell induction in the intestine, this suggests a different biology for the distal pulmonary tuft cells, although the inflammation-associated biology of the corresponding tracheal tuft cells has not been established. Somewhat surprisingly, tuft cell deficient mice do not develop abnormalities of alveolar regeneration following influenza and similarly, mucous metaplasia, which is associated with type 2 inflammation, was unchanged in the tuft cell deficient mice. Although the major findings of the study are negative, it provides important new information on these enigmatic cells.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1, Reviewer #2 and Reviewer #3 agreed to share their name with the authors. This manuscript was co-submitted with: https://www.biorxiv.org/content/10.1101/2022.03.11.483948v1)

Evaluation Summary:

Sphingomyelin synthase 2 (SMS2) is a Golgi-localized enzyme that synthesizes sphingomyelin, a critical lipid in the plasma membrane, and mutations in SMS2 underly a rare genetic disorder of bone formation. This study shows that the disease mutations cause retention of SMS2 in the ER, which leads to sphingomyelin being produced in the wrong place and thus to a disrupted sphingomyelin and cholesterol gradient in the membranes of the secretory pathway. Additional experiments would improve the impact of this study in explaining the underlying reasons for some bone development disorders and providing cell biologists with new tools to manipulate lipids in cells.

(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)