Cell Biology

When mitochondria fall apart: Unbalanced mitochondrial segregation triggers loss of mtDNA in the absence of mitochondrial fusion

1. Lisa Dengler
2. Francesco Padovani
3. Bianca Lemke
4. Rebecca Brugger
5. Benedikt Westermann
6. Boris Maček
7. Kurt M. Schmoller
8. Jennifer C. Ewald

Reviewed by Review Commons

A GCN1-independent activator of the kinase GCN2

1. JiaYi Zhu
2. Giulia Emanuelli
3. Glenn R Masson
4. Vanesa Vinciauskaite
5. Henriette Willems
6. Andrew Lim
7. Christopher Alan Brown
8. David Winpenny
9. Murray Clarke
10. Rebecca Gilley
11. Fergus Preston
12. Jordan Wilson
13. Aldo Bader
14. Taufiq Rahman
15. Joseph E Chambers
16. John Skidmore
17. Nicholas W Morrell
18. Stefan J Marciniak

• Curated by eLife

  eLife Assessment

  This study presents a screen for small-molecule activators of the kinase GCN2 that phosphorylates the eukaryotic translation initiation factor 2 alpha (eIF2α) in response to diverse stress stimuli. Among the compounds identified, one stands out as a potent activator that functions independently of GCN1, which is important for probing mechanisms of Integrated Stress Response regulation and may have translational relevance in the context of pathogenic GCN2 mutations. While some reviewers found the biochemical analyses convincing, others viewed the cellular evidence as limited, particularly with respect to time points, endogenous readouts, and broader cell-type validation, which prevents a clear assessment of the compound's potential potency in a physiological context.

Reviewed by eLife

The fate of pyruvate dictates cell growth by modulating cellular redox potential

1. Ashish G Toshniwal
2. Geanette Lam
3. Alex J Bott
4. Ahmad A Cluntun
5. Rachel Skabelund
6. Hyuck-Jin Nam
7. Dona R Wisidagama
8. Carl S Thummel
9. Jared Rutter

• Curated by eLife

  eLife Assessment

  This fundamental work demonstrates that compartmentalized cellular metabolism is a dominant input into cell size control in a variety of mammalian cell types and in Drosophila. The authors show that increased pyruvate import into the mitochondria in liver-like cells and in primary hepatocytes drives gluconeogenesis but reduces cellular amino acid production, suppressing protein synthesis. The evidence supporting the conclusions is compelling, with a variety of genetic and pharmacologic assays rigorously testing each step of the proposed mechanism. This work will be of interest to cell biologists, physiologists, and researchers interested in cell metabolism, and is significant because stem cells and many cancers exhibit metabolic rewiring of pyruvate metabolism.

Reviewed by eLife

Targeting RhoA activity rejuvenates aged hematopoietic stem cells

1. Eva Mejía-Ramírez
2. Pablo Iañez Picazo
3. Barbara Walter
4. Sara Montserrat-Vazquez
5. Francesco Affuso
6. Stefan Wieser
7. Fabio Pezzano
8. Loïc Reymond
9. Jorge Castillo-Robles
10. Francesca Matteini
11. Loris Mularoni
12. Dídac Maciá
13. Ángel Raya
14. Verena Ruprecht
15. Yi Zheng
16. Paula Petrone
17. M. Carolina Florian

Reviewed by preLights

The Rab7-Epg5 and Rab39-ema modules cooperatively position autophagosomes for efficient lysosomal fusions

1. Attila Boda
2. Villő Balázs
3. Anikó Nagy
4. Dávid Hargitai
5. Mónika Lippai
6. Zsófia Simon-Vecsei
7. Márton Molnár
8. Fanni Fürstenhoffer
9. Gábor Juhász
10. Péter Lőrincz

• Curated by eLife

  eLife Assessment

  This paper presents valuable findings on how autophagosomes are positioned along microtubules for their efficient fusion with lysosomes, providing significant insights into the mechanism. The evidence supporting the conclusions is solid, with high-quality fluorescence microscopy combined with Drosophila genetics. This work will be of broad interest to cell biologists interested in autophagy and related cell biology fields.

Reviewed by eLife

Calcium transfer from the ER to other organelles for optimal signaling in Toxoplasma gondii

1. Zhu-Hong Li
2. Beejan Asady
3. Le Chang
4. Myriam Andrea Hortua Triana
5. Catherine Li
6. Isabelle Coppens
7. Silvia NJ Moreno

• Curated by eLife

  eLife Assessment

  This important study shows that calcium stores in the endoplasmic reticulum of the parasitic protozoan, Toxoplasma gondii play a major role in buffering calcium levels in the cytosol as well as other organelles such as the mitochondrion. Advanced imaging techniques, including use of genetically encoded calcium indicators provide compelling evidence for the role of the SERCA-Ca2+ ATPase pump in regulating organellar calcium levels. However, it remains unclear whether intra-organellar calcium transport occurs via ER-mitochondria membrane contact sites or other mechanisms. This work will be of interest to cell and molecular biologists interested in calcium signalling in divergent eukaryotes.

Reviewed by eLife

Treacle and MDC1 coordinate rDNA break repair by homologous recombination

1. Andrea Haenel
2. Johannes Leyrer
3. Manuel Stucki

• Curated by eLife

  eLife Assessment

  This manuscript reports valuable results on the role of MDC1 and Treacle in DSB repair in rDNA repeats. It has been previously established that MDC1 is replaced by Treacle as the main adaptor in the nucleolar DNA damage response. This work provides convincing evidence that MDC1 is required for the recruitment of RAD51 and BRCA1 to DSBs in rDNA. The work involves multiple MDC1 knockout models and establishes that RFN8-RNF168 act downstream of MDC1 in the recruitment of the HR machinery to nucleolar DSBs.

Reviewed by eLife

Aging-associated Increase of GATA4 levels in Articular Cartilage is Linked to Impaired Regenerative Capacity of Chondrocytes and Osteoarthritis

1. Meagan J Makarczyk
2. Yiqian Zhang
3. Alyssa Aguglia
4. Olivia Bartholomew
5. Sophie Hines
6. Kate Li
7. Suyash Sinkar
8. Silvia Liu
9. Craig Duvall
10. Hang Lin

• Curated by eLife

  eLife Assessment

  This study presents an important finding on the role of GATA4 in aging- and OA-associated cartilage pathology. The conclusions are well supported by compelling in vitro and in vivo evidence. This work will be of broad interest to both cell biologists and orthopedic/skeletal health clinicians.

Reviewed by eLife

Paclitaxel compromises nuclear integrity in interphase through SUN2-mediated cytoskeletal coupling

1. Thomas Hale
2. Victoria L. Hale
3. Piotr Kolata
4. Ália dos Santos
5. Matteo Allegretti

Reviewed by preLights, Review Commons

Dissociation of the nuclear basket triggers chromosome loss in aging yeast

1. Mihailo Mirkovic
2. Jordan McCarthy
3. Anne Cornelis Meinema
4. Julie Parenteau
5. Sung Sik Lee
6. Sherif Abou Elela
7. Yves Barral

• Curated by eLife

  eLife Assessment

  This fundamental study reveals that aging in yeast leads to chromosome mis-segregation due to asymmetric partitioning of chromosomes, driven by disruption of the nuclear pore complex and pre-mRNA leakage. The findings are convincingly supported by carefully-designed experimental data with a combination of genetic, molecular biology and cell biology approaches.

Reviewed by eLife