Cell Biology

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

Anti-resonance in developmental signaling regulates cell fate decisions

1. Samuel J Rosen
2. Olivier Witteveen
3. Naomi Baxter
4. Ryan S Lach
5. Erik Hopkins
6. Marianne Bauer
7. Maxwell Z Wilson

• Curated by eLife

  eLife Assessment

  This important work combines theoretical analysis with precise experimental perturbation to demonstrate that the Wnt signaling pathway is characterized by anti-resonance, or a suppression of pathway output at intermediate activation frequencies. The authors identify an anti-resonance behavior, with compelling evidence from optogenetic stimulation in multiple cell types, alongside modeling results that corroborate the phenomenon. While the demonstration of this phenomenon has yet to be extended to fully physiological situations, its clear existence within optogenetically stimulated systems shows that it is likely a significant factor that contributes to the behavior of this central signaling pathway.

Reviewed by eLife

Condensation of Sidekick at tricellular junctions organizes mechanical forces for cell-cell adhesion remodeling

1. Hiroyuki Uechi
2. Daxiao Sun
3. Yuki Saeki
4. Tetsuya Hiraiwa
5. Alf Honigmann
6. Anthony A. Hyman
7. Erina Kuranaga

Reviewed by preLights

THE FAM53C/DYRK1A axis regulates the G1/S transition of the cell cycle

1. Taylar Hammond
2. Jong Bin Choi
3. Miles W. Membreño
4. Janos Demeter
5. Roy Ng
6. Debadrita Bhattacharya
7. Thuyen N. Nguyen
8. Griffin G. Hartmann
9. Caterina I Colón
10. Carine Bossard
11. Jan M. Skotheim
12. Peter K. Jackson
13. Anca Pasca
14. Seth M. Rubin
15. Julien Sage

Reviewed by Review Commons

Compromised DNA replication in gut cells underlies tardigrade sensitivity to genotoxic stress

1. Gonzalo Quiroga-Artigas
2. Pauline Fontanié
3. Benjamin Lacroix
4. Maria Dolores Molina
5. María Moriel-Carretero

Reviewed by Review Commons