Cell Biology

Acidocalcisome-like vacuoles constitute a feedback-controlled phosphate buffering system for the cytosol

1. Samuel Bru
2. Lydie Michaillat Mayer
3. Geun-Don Kim
4. Danye Qiu
5. Henning J Jessen
6. Andreas Mayer

• Curated by eLife

  eLife Assessment

  This study provides fundamental insights into eukaryotic phosphate homeostasis by demonstrating how yeast vacuoles dynamically regulate cytosolic phosphate levels. The conclusions are convincing, supported by an elegant combination of in vitro assays and in vivo measurements. This study will be of interest to cell biologists, particularly for those who are working in the field of phosphate metabolism.

Reviewed by eLife

Labeling of Nascent RNA in C. elegans Intestine

1. Omid Gholamalamdari
2. Stephanie C. Weber

Reviewed by Arcadia Science

SMC5/6-mediated plasmid silencing is directed by SIMC1–SLF2 and antagonized by the SV40 large T antigen

1. Martina Oravcová
2. Minghua Nie
3. Takanori Otomo
4. Michael N Boddy

• Curated by eLife

  eLife Assessment

  This Research Advance manuscript further elucidates the roles of SMC5/6 loader proteins and associated factors in the silencing of extrachromosomal circular DNA by the SMC5/6 complex. While the findings are largely in line with expectations, they are valuable, representing a meaningful advance beyond the recent study from the same laboratories (PMC9708086), validating the previous model that distinct SMC5/6 subcomplexes, SIMC1-SLF2 and SLF1/2, separately control its transcriptional repression and DNA repair activities on extrachromosomal DNA. Solid evidence is presented for a role for SIMC1/SLF2 in localization of the SMC5/6 complex to plasmid DNA, and the distinct requirements as compared to recruitment of SMC5/6 to chromosomal DNA lesions.

Reviewed by eLife

Vesiculation pathways in clathrin-mediated endocytosis

1. Xinran Wang
2. Julien Berro
3. Rui Ma

• Curated by eLife

  eLife Assessment

  This valuable study proposes a theoretical model of clathrin coat formation based on membrane elasticity that seeks to determine whether this process occurs by increasing the area of a protein-coated patch with constant curvature, or by increasing the curvature of a protein-coated patch that forms in an initially flat conformation (so called constant curvature or constant area models). Identifying energetically favorable pathways and comparing the obtained shapes with experiments provides solid support to the constant-area pathway. This work will be of interest for biologists and biophysicists interested in membrane remodelling and endocytosis. It provides an innovative approach to tackle the question of constant curvature vs. constant area coat protein formation, although some of the model's assumption are only partially supported by experimental evidence.

Reviewed by eLife

Abnormal shear stress induces ferroptosis in endothelial cells via KLF6 downregulation

1. Jingang Cui
2. Zhiyu Fan
3. Suoqi Ding
4. Jiazhen Zhang
5. Huihong Shen
6. Syeda Armana Zaidi
7. Yongsheng Ding

• Curated by eLife

  eLife Assessment

  This study presents valuable findings on the role of KLF6 in in vitro endothelial cells exposed to altered (high or low) shear stress with a customized microfluidic device to investigate mechanisms of atherosclerosis. The finding that altered shear stress results in endothelial cell ferroptosis through reduced expression of KLF6 is compelling and adds a new layer of complexity to the pathogenesis of atherosclerotic plaques. However, the inclusion of an arterial cell line and re-evaluation of the statistical tests used would strengthen the authors' conclusions.

Reviewed by eLife

Axonal distribution of mitochondria maintains neuronal autophagy during aging via eIF2β

1. Kanako Shinno
2. Yuri Miura
3. Koichi M Iijima
4. Emiko Suzuki
5. Kanae Ando

• Curated by eLife

  eLife Assessment

  In flies defective for axonal transport of mitochondria, the authors report the upregulation of one subunit, the beta subunit, of the heterotrimeric eIF2 complex via mass spectroscopy proteomics. Neuronal overexpression of eIF2β phenocopied aspects of neuronal dysfunction observed when axonal transport of mitochondria was compromised. Conversely, lowering eIF2β expression suppressed aspects of neuronal dysfunction. While these are intriguing and useful observations, technical weaknesses limit the interpretation. On balance, the evidence supporting the current claims is suggestive but incomplete, especially concerning the characterization of the eIF2 heterotrimer and the data regarding translational regulation.

Reviewed by eLife

Accessibility of the unstructured α-tubulin C-terminal tail is controlled by microtubule lattice conformation

1. Takashi Hotta
2. Morgan L Pimm
3. Ezekiel C Thomas
4. Yang Yue
5. Patrick DeLear
6. Lynne Blasius
7. Michael Cianfrocco
8. Morgan DeSantis
9. Ryota Horiuchi
10. Takumi Higaki
11. David Sept
12. Ryoma Ohi
13. Kristen J Verhey

• Curated by eLife

  eLife Assessment

  This fundamental work reveals that the accessibility of the unstructured C-terminal tails of α- and β-tubulins differs with the state of the microtubule lattice. Their accessibility increases with the expansion of the lattice induced by GTP and certain MAPs, which can then dictate the subsequent interactions between MAPs and microtubules, and post-translational modifications of tubulin tails. The evidence supporting the conclusion is compelling, although the characterisation of the probes does not answer whether they directly affect the lattice or expose the C-terminal tails of tubulin. This work will be of great interest to the cytoskeleton field.

Reviewed by eLife

Mechanotransductive feedback control of endothelial cell motility and vascular morphogenesis

1. Devon E Mason
2. Paula Camacho
3. Megan E Goeckel
4. Brendan R Tobin
5. Sebastián L Vega
6. Pei-Hsun Wu
7. Dymonn Johnson
8. Su-Jin Heo
9. Denis Wirtz
10. Jason A Burdick
11. Levi Wood
12. Brian Y Chow
13. Amber N Stratman
14. Joel D Boerckel

• Curated by eLife

  eLife Assessment

  This fundamental study substantially advances our current understanding of mechanotransduction within endothelial cells. The evidence provided by the authors in the revised manuscript is compelling, which taken together, provides strong support for the authors' major findings. The work will be of broad interest to cell biologists and vascular biologists.

Reviewed by eLife

Dominant spinal muscular atrophy linked mutations in the cargo binding domain of BICD2 result in altered interactomes and dynein hyperactivity

1. Hannah Neiswender
2. Jessica E Pride
3. Rajalakshmi Veeranan-Karmegam
4. Phylicia Allen
5. Grace Neiswender
6. Avneesh Prabakar
7. Caili Hao
8. Xingjun Fan
9. Graydon B Gonsalvez

• Curated by eLife

  eLife Assessment

  In their study, Neiswender et al. provide important insights into how BicD2 variants linked to spinal muscular atrophy alter dynein activity and cargo specificity. The authors present convincing evidence that disease-associated mutations lead to interactome changes, supported by additional validation of the BicD2/HOPS complex and discussion of their functional implications. This well-executed study offers invaluable datasets and a strong foundation for future exploration of disease mechanisms.

Reviewed by eLife

Suppression of interferon signaling via small molecule modulation of TFAM

1. Dionisia P Sideris
2. Hsuan Lee
3. Lyndsay Olson
4. Kalyan Nallaparaju
5. Keiichiro Okuyama
6. Jeff Ciavarri
7. Robert Lafyatis
8. Mads B Larsen
9. Bo Lin
10. Irene Alfaras
11. Jason R Kennerdell
12. Toren Finkel
13. Yuan Liu
14. Bill B Chen
15. Lin Lyu

• Curated by eLife

  eLife Assessment

  Using high-throughput small-molecule screening, this study discloses novel modulators of the mitochondrial transcription factor A (TFAM), a key regulator of mitochondrial function. Reviewers viewed the targeting of TFAM as innovative and the study's conclusions as potentially important (especially the effects on inflammation). However, the lack of evidence for a direct effect of the compounds on TFAM activity weakens the paper's key conclusion and renders the study incomplete.

Reviewed by eLife