Biochemistry

The UbiB family member Cqd1 forms a novel membrane contact site in mitochondria

1. Siavash Khosravi
2. Xenia Chelius
3. Ann-Katrin Unger
4. Daniela Rieger
5. Johanna Frickel
6. Timo Sachsenheimer
7. Christian Lüchtenborg
8. Rico Schieweck
9. Britta Brügger
10. Benedikt Westermann
11. Till Klecker
12. Walter Neupert
13. Max E. Harner

Reviewed by Review Commons

Cytosolic aspartate aminotransferase moonlights as a ribosome-binding modulator of Gcn2 activity during oxidative stress

1. Robert A Crawford
2. Mark P Ashe
3. Simon J Hubbard
4. Graham D Pavitt

• Curated by eLife

  Evaluation Summary:

  Using mass spectrometry, Crawford et al. identify aspartate aminotransferase 2 (Aat2) as a protein whose polysome-association is increased under oxidative stress in yeast. Aat2 deletion sensitizes yeast to oxidative stress, which is paralleled by an aberrantly elevated integrated stress response, although polysome-association of Aat2 and its effect on oxidative stress response are independent of its aminotransferase activity. This provides evidence that metabolic enzymes may "moonlight" as post-transcriptional regulators. The study will appeal to experts in the fields of biochemistry, genetics, cellular and molecular biology. The presented data mostly support the authors' conclusions, but there are a few technical issues that should be addressed. These include corroborating Aat2:ribosome association and characterizing the effects of non-catalytic Aat2 mutants on the integrated stress response.

  (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 3 agreed to share their name with the authors.)

Reviewed by eLife

Mitochondrial redox adaptations enable alternative aspartate synthesis in SDH-deficient cells

1. Madeleine L Hart
2. Evan Quon
3. Anna-Lena BG Vigil
4. Ian A Engstrom
5. Oliver J Newsom
6. Kristian Davidsen
7. Pia Hoellerbauer
8. Samantha M Carlisle
9. Lucas B Sullivan

• Curated by eLife

  Evaluation Summary:

  Hart et al show that loss of mitochondrial complex I rescues succinate dehydrogenase deficient (SDH) cells. The experiments are well performed and the phenotype is potentially very interesting to researchers of cancer metabolism. The authors propose that rescue of SDH deficiency by complex I inhibition is caused by an increase in mitochondrial NADH which leads to a restoration of aspartate levels, which in turn rescues proliferation. To support the model, the authors do demonstrate that there are possible correlations of this phenotype to restored aspartate biosynthesis. However, they do not unambiguously establish a mechanism that fully defines how complex I inhibition rescues the proliferation of SDH deficient 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.)

Reviewed by eLife

Biochemical and structural insights into SARS-CoV-2 polyprotein processing by Mpro

1. Ruchi Yadav
2. Valentine V. Courouble
3. Sanjay K. Dey
4. Jerry Joe E. K. Harrison
5. Jennifer Timm
6. Jesse B. Hopkins
7. Ryan L. Slack
8. Stefan G. Sarafianos
9. Francesc X. Ruiz
10. Patrick R. Griffin
11. Eddy Arnold

Reviewed by ScreenIT

Filamentation modulates allosteric regulation of PRPS

1. Huan-Huan Hu
2. Guang-Ming Lu
3. Chia-Chun Chang
4. Yilan Li
5. Jiale Zhong
6. Chen-Jun Guo
7. Xian Zhou
8. Boqi Yin
9. Tianyi Zhang
10. Ji-Long Liu

• Curated by eLife

  Evaluation Summary:

  The authors investigated the structure of phosphoribosyl pyrophosphate (PRPP) synthase (PRPPS) from Escherichia coli, a highly conserved enzyme from bacteria to mammals that catalyzes the synthesis of a key common compound for several metabolic pathways. Combining structural data with mutagenesis and activity assays, they demonstrate that the enzyme is regulated differently by allosteric effectors when assembled into one filament form or the other. The strength of the manuscript is the high-quality cryo-EM data, which allows the reconstruction of two different filament forms bound to different ligands.

  (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.)

Reviewed by eLife

Structural basis of a two-antibody cocktail exhibiting highly potent and broadly neutralizing activities against SARS-CoV-2 variants including diverse Omicron sublineages

1. Xiaoman Li
2. Yongbing Pan
3. Qiangling Yin
4. Zejun Wang
5. Sisi Shan
6. Laixing Zhang
7. Jinfang Yu
8. Yuanyuan Qu
9. Lina Sun
10. Fang Gui
11. Jia Lu
12. Zhaofei Jing
13. Wei Wu
14. Tao Huang
15. Xuanling Shi
16. Jiandong Li
17. Xinguo Li
18. Dexin Li
19. Shiwen Wang
20. Maojun Yang
21. Linqi Zhang
22. Kai Duan
23. Mifang Liang
24. Xiaoming Yang
25. Xinquan Wang

Reviewed by ScreenIT

Molecular Investigations of Selected Spike Protein Mutations in SARS-CoV-2: Delta and Omicron Variants and Omicron Subvariants

1. Urmi Roy

Reviewed by ScreenIT

The orphan ligand, activin C, signals through activin receptor-like kinase 7

1. Erich J Goebel
2. Luisina Ongaro
3. Emily C Kappes
4. Kylie Vestal
5. Elitza Belcheva
6. Roselyne Castonguay
7. Ravindra Kumar
8. Daniel J Bernard
9. Thomas B Thompson

• Curated by eLife

  Evaluation Summary:

  This study was designed to examine the orphan ligand ActivinC. The authors show that ActivinC signals through ALK7. The data presented are strong and convincing. Indeed, the use of purified proteins for the interaction assays and in vivo analysis of adipocytes provide considerable rigor to the analysis. The work will be of interest to the areas of signal transduction and drug design.

  (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.)

Reviewed by eLife

Structure-activity relationships of mitochondria-targeted tetrapeptide pharmacological compounds

1. Wayne Mitchell
2. Jeffrey D Tamucci
3. Emery L Ng
4. Shaoyi Liu
5. Alexander V Birk
6. Hazel H Szeto
7. Eric R May
8. Andrei T Alexandrescu
9. Nathan N Alder

• Curated by eLife

  Evaluation Summary:

  Wayne Mitchell et al. report the study aimed to determine the structural features of cationic hydrophobic tetrapeptides in their cytoprotective efficacy. Detailed structural characterization of the peptides "free" in solution and bound to membranes is followed by their comparison in protecting cells from starvation-induced stress and the loss of viability. Overall, there are important and detailed observations regarding the peptide-membrane interactions, while their relevance to cytoprotection mechanisms in not demonstrated.

  (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.)

Reviewed by eLife

Reconstitution of the SARS-CoV-2 ribonucleosome provides insights into genomic RNA packaging and regulation by phosphorylation

1. Christopher R. Carlson
2. Armin N. Adly
3. Maxine Bi
4. Conor J. Howard
5. Adam Frost
6. Yifan Cheng
7. David O. Morgan

Reviewed by ScreenIT