Molecular Biology

Inhibition of mitochondrial protein import and proteostasis by a pro-apoptotic lipid

1. Josep Fita-Torró
2. José Luis Garrido-Huarte
3. Lucía López-Gil
4. Agnès H Michel
5. Benoit Kornmann
6. Amparo Pascual-Ahuir
7. Markus Proft

• Curated by eLife

  eLife Assessment

  This study is a valuable observation that deals with the toxic effects of an intermediary in lipid degradation [trans-2-hexadecenal (t-2-hex)] in yeast through modification of mitochondrial protein import via the TOM complex. We find that the claim that the TOM complex is a main target of t-2-hex are supported by solid evidence, however the molecular mechanism remains unclear allowing multiple interpretation. Despite the shortcomings, this study is inspiring for researchers from the organellar, protein trafficking and lipid field and serves as a starting point to further precise and mechanistic analyses of the phenomenon.

Reviewed by eLife

Nitrosation of CD36 Regulates Endothelial Function and Serum Lipids

1. Melissa A. Luse
2. Wyatt J. Schug
3. Luke S. Dunaway
4. Shruthi Nyshadham
5. Skylar A. Loeb
6. Alicia Carvalho
7. Rachel Tessema
8. Caitlin Pavelec
9. T.C. Stevenson Keller
10. Xiaohong Shu
11. Claire A. Ruddiman
12. Anna Kosmach
13. Timothy M. Sveeggen
14. Ray Mitchell
15. Pooneh Bagher
16. Richard D. Minshall
17. Norbert Leitnger
18. Linda Columbus
19. Kandice R. Levental
20. Ilya Levental
21. Miriam Cortese-Krott
22. Brant E. Isakson

Reviewed by Life Science Editors Foundation

SIRT6 activator fucoidan extends healthspan and lifespan in aged wild-type mice

1. Seyed A. Biashad
2. Eric Hillpot
3. Francesco Morandini
4. Cheyenne Rechsteiner
5. Victoria Paige
6. Gregory Tombline
7. Minseon Lee
8. Zhizhong Zheng
9. Yuan Liang
10. John Martinez
11. Natasha Sieczkiewicz
12. Zhihui Zhang
13. Valentin Volobaev
14. Denis Firsanov
15. Matthew Simon
16. Lei J. Zhang
17. Paul D. Robbins
18. Andrei Seluanov
19. Vera Gorbunova

Reviewed by Life Science Editors Foundation

Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions

1. Leonor Miller-Fleming
2. Wing Hei Au
3. Laura Raik
4. Pedro Guiomar
5. Jasper Schmitz
6. Ha Yoon Cho
7. Aron Czako
8. Alexander J Whitworth

Reviewed by Review Commons

In silico screening by AlphaFold2 program revealed the potential binding partners of nuage-localizing proteins and piRNA-related proteins

1. Shinichi Kawaguchi
2. Xin Xu
3. Takashi Soga
4. Kenta Yamaguchi
5. Ryuuya Kawasaki
6. Ryota Shimouchi
7. Susumu Date
8. Toshie Kai

• Curated by eLife

  eLife Assessment

  This useful study employs AlphaFold2 to predict interactions among 20 nuage proteins, identifying five novel interaction candidates, three of which are validated experimentally through co-immunoprecipitation. Expanding the analysis to 430 oogenesis-related proteins and screening ~12,000 Drosophila proteins for interactions with Piwi, the study identifies 164 potential binding partners, demonstrating how computational predictions can streamline experimental validation. This study provides a solid basis for further investigations into eukaryotic protein interaction networks.

Reviewed by eLife

Optogenetic control of Protein Kinase C-epsilon activity reveals its intrinsic signaling properties with spatiotemporal resolution

1. Qunxiang Ong
2. Crystal Jing Yi Lim
3. Yilie Liao
4. Justin Tze-Yang Ng
5. Ler Ting Rachel Lim
6. Shernys Xuan Yi Koh
7. Sher En Chan
8. Pheobe Lee Yu Ying
9. Huijun Lim
10. Chen Rui Ye
11. Loo Chien Wang
12. Siok Ghee Ler
13. Radoslaw M Sobota
14. Yaw Sing Tan
15. Gerald I Shulman
16. Xiaoyong Yang
17. Weiping Han

• Curated by eLife

  eLife Assessment

  This manuscript introduces Opto-PKCε, an optogenetic tool that enabled important findings derived from interactome and phosphoproteome studies. Light-dependent recruitment of Opto-PKCε to the plasma membrane revealed the specific phosphorylation of the insulin receptor at Thr 1160. In turn, recruitment to mitochondria led to phosphorylation of the complex I subunit NDUFS4, correlating with reduced spare respiratory capacity. The evidence supporting these conclusions is solid, although additional clarification on data analysis would further enhance readability.

Reviewed by eLife

Acute Activation of Genes Through Transcriptional Condensates Impact Non-target Genes in a Chromatin Domain

1. Darshika Bohra
2. Zubairul Islam
3. Sundarraj Nidharshan
4. Aprotim Mazumder
5. Dimple Notani

• Curated by eLife

  eLife Assessment

  The authors use single molecule imaging and in vivo loop-capture genomic approaches to investigate estrogen mediated enhancer-target gene activation in human cancer cells. These potentially important results suggest that ER-alpha can, in a temporal delay, activate a non-target gene TFF3, which is in proximity to the main target gene TFF1, even though the estrogen responsive enhancer does not loop with the TFF3 promoter. To explain these results, the authors invoke a transcriptional condensate model. The claim of a temporal delay and effects of the target gene transcription on the non-target gene expression are supported by solid evidence but there is no direct evidence of the role of a condensate in mediating this effect. The reviewers appreciate that the authors have done a lot of work to strengthen the study. This work will be of interest to those studying transcriptional gene regulation and hormone-aggravated cancers.

Reviewed by eLife

MagIC-Cryo-EM, structural determination on magnetic beads for scarce macromolecules in heterogeneous samples

1. Yasuhiro Arimura
2. Hide A Konishi
3. Hironori Funabiki

• Curated by eLife

  eLife Assessment

  This study follows up on Arimura et al's powerful new method MagIC-Cryo-EM for imaging native complexes at high resolution. Using a clever design embedding protein spacers between the antibody and the nucleosomes purified, thereby minimizing interference from the beads, the authors concentrate linker histone variant H1.8 containing nucleosomes. From these samples, the authors obtain convincing atomic structures of the H1.8 bound chromatosome purified from interphase and metaphase cells, finding a NPM2 chaperone bound form exists as well. Caveats previously noted have been addressed nicely in the revision, strengthening the overall conclusions. This is an important new tool in the arsenal of single molecule biologists, permitting a deep dive into structure of native complexes, and will be of high interest to a broad swathe of scientists studying native macromolecules present at low concentrations in cells.

Reviewed by eLife

Transcriptomic meta-analysis in plaque psoriasis: an integrative bioinformatic approach to deciphering the genetic landscape and molecular pathways

1. Teresa Torres-Moral
2. Josep Riera-Monroig
3. Gemma Tell-Martí
4. Jaume Bagué
5. José F. Català-Senent
6. Francisco J. Roig
7. Míriam Potrony
8. Francisco García-García
9. Susana Puig

Reviewed by Arcadia Science

Small-molecule activation of TFEB alleviates Niemann–Pick disease type C via promoting lysosomal exocytosis and biogenesis

1. Kaili Du
2. Hongyu Chen
3. Zhaonan Pan
4. Mengli Zhao
5. Shixue Cheng
6. Yu Luo
7. Wenhe Zhang
8. Dan Li

• Curated by eLife

  eLife Assessment

  This study reports that activation of TFEB promotes lysosomal exocytosis and clearance of cholesterol from lysosomes, the strength of evidence for which is convincing with appropriate and validated methodology in line with current state-of-the-art. The significance of the findings is important in the context of Niemann-Pick Disease Type C as well as other subfields.

Reviewed by eLife