Biochemistry

The deubiquitinase Ubp3/Usp10 constrains glucose-mediated mitochondrial repression via phosphate budgeting

1. Vineeth Vengayil
2. Shreyas Niphadkar
3. Swagata Adhikary
4. Sriram Varahan
5. Sunil Laxman

• Curated by eLife

  eLife assessment

  This study provides valuable insights into the regulation of metabolic flux between glycolysis and respiration in yeast, particularly focusing on the role of inorganic phosphate. The authors propose a novel mechanism involving Ubp3/Ubp10 that potentially mitigates the Crabtree effect, offering substantial, solid evidence through a variety of well-designed assays. This study could reshape our understanding of metabolic regulation with broad biological contexts.

Reviewed by eLife

Reassessing the substrate specificities of the major Staphylococcus aureus peptidoglycan hydrolases lysostaphin and LytM

1. Lina Antenucci
2. Salla Virtanen
3. Chandan Thapa
4. Minne Jartti
5. Ilona Pitkänen
6. Helena Tossavainen
7. Perttu Permi

• Curated by eLife

  eLife assessment

  This manuscript describes a valuable study aimed at identifying the substrate specificity of two cell wall hydrolases LSS and LytM in S. aureus. The authors show that LytM has a novel function of cleaving D-Ala-Gly instead of only Gly-Gly by using synthetic substrates and compelling NMR-based real-time kinetics measurements.

Reviewed by eLife

Biochemical and neurophysiological effects of deficiency of the mitochondrial import protein TIMM50

1. Eyal Paz
2. Sahil Jain
3. Irit Gottfried
4. Orna Staretz-Chacham
5. Muhammad Mahajnah
6. Pritha Bagchi
7. Nicholas T. Seyfried
8. Uri Ashery
9. Abdussalam Azem

• Curated by eLife

  eLife assessment

  This valuable study presents interesting results aimed at explaining the effects of a human mutation on the mitochondrial import protein TIMM50 on mitochondrial function and neuronal excitability. While the evidence supporting the conclusions is solid, the interpretation of some of the results requires revision and moderation. This paper will be of interest to scientists in the mitochondria field.

Reviewed by eLife

Intramolecular feedback regulation of the LRRK2 Roc G domain by a LRRK2 kinase dependent mechanism

1. Bernd K Gilsbach
2. Franz Y Ho
3. Benjamin Riebenbauer
4. Xiaojuan Zhang
5. Giambattista Guaitoli
6. Arjan Kortholt
7. Christian Johannes Gloeckner

• Curated by eLife

  eLife assessment

  This valuable manuscript reports on the relationship between GTP hydrolysis parameters and kinase activity of LRRK2, which is associated with Parkinson's disease. The authors provide a detailed accounting of the catalytic efficiency of the ROC GTPase domain of pathogenic variants of LRRK2, in comparison with the wild-type enzyme. The authors propose that phosphorylation of T1343 inhibits kinase activity and influences monomer-dimer transitions, but the experimental evidence is currently incomplete.

Reviewed by eLife

Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis

1. Amanda Mixon Blackwell
2. Yasaman Jami-Alahmadi
3. Armiyaw S. Nasamu
4. Shota Kudo
5. Akinobu Senoo
6. Celine Slam
7. Kouhei Tsumoto
8. James A. Wohlschlegel
9. Jose M. M. Caaveiro
10. Daniel E. Goldberg
11. Paul A. Sigala

• Curated by eLife

  eLife assessment

  This important study reveals that the malaria parasite protein PfHO, though lacking typical heme oxygenase activity, is vital for the survival of Plasmodium falciparum. Structural and localization analyses showed that PfHO is essential for apicoplast maintenance, particularly in gene expression and biogenesis, indicating a novel adaptive role for this protein in parasite biology. While the results supporting the claims of the authors are convincing, the lack of data defining a molecular understanding or mechanism of action of the protein in question limits the impact of the study.

Reviewed by eLife

Direct observation of fluorescent proteins in gels: a rapid cost-efficient, and quantitative alternative to immunoblotting

1. Matthieu Sanial
2. Ryan Miled
3. Marine Alves
4. Sandra Claret
5. Nicolas Joly
6. Véronique Proux-Gillardeaux
7. Anne Plessis
8. Sébastien Léon

Reviewed by Review Commons

Allosteric inhibition of trypanosomatid pyruvate kinases by a camelid single-domain antibody

1. Joar Esteban Pinto Torres
2. Mathieu Claes
3. Rik Hendrickx
4. Meng Yuan
5. Natalia Smiejkowska
6. Pieter Van Wielendaele
7. Hans De Winter
8. Serge Muyldermans
9. Paul A Michels
10. Malcolm D Walkinshaw
11. Wim Versées
12. Guy Caljon
13. Stefan Magez
14. Yann G.-J Sterckx

• Curated by eLife

  eLife assessment

  This work presents valuable data demonstrating that a camelid single-domain antibody can selectively inhibit a key glycolytic enzyme in trypanosomes via an allosteric mechanism. The claim that this information can be exploited for the design of novel chemotherapeutics is incomplete and limited by the modest effects on parasite growth, as well as the lack of evidence for cellular target engagement in vivo.

Reviewed by eLife

Mag-Net: Rapid enrichment of membrane-bound particles enables high coverage quantitative analysis of the plasma proteome

1. Christine C. Wu
2. Kristine A. Tsantilas
3. Jea Park
4. Deanna Plubell
5. Justin A. Sanders
6. Previn Naicker
7. Ireshyn Govender
8. Sindisiwe Buthelezi
9. Stoyan Stoychev
10. Justin Jordaan
11. Gennifer Merrihew
12. Eric Huang
13. Edward D. Parker
14. Michael Riffle
15. Andrew N. Hoofnagle
16. William S. Noble
17. Kathleen L. Poston
18. Thomas J. Montine
19. Michael J. MacCoss

Reviewed by PREreview

A unique cell division protein critical for the assembly of the bacterial divisome

1. Xiao Chu
2. Lidong Wang
3. Yiheng Zhu
4. Zhengshan Feng
5. Qingtian Guan
6. Lei Song
7. Zhaoqing Luo

• Curated by eLife

  eLife assessment:

  This useful study shows that the essential Acinetobacter baumannii gene Aeg1 likely plays an key role in cell division. The strength of the work is the discovery that the depletion of Aeg1 leads to cell filamentation and that gain-of-function mutations in cell division genes FtsB and FtsL rescue the lethality of Aeg1 depletion. However, Aeg1's localization pattern and its requirement for other division proteins' localizations require further characterization of the functionality of fluorescent fusion proteins, fluorescence images of higher quality, and improvements in statistic qualifications, leaving the study' evidence for Aeg1's exact role in cell division incomplete at this time. In conclusion, the critical role of Aeg1 in the assembly of the A. baumannii divisome has yet to be established unambiguously.

Reviewed by eLife, Arcadia Science

Activation of polycystin-1 signaling by binding of stalk-derived peptide agonists

1. Shristi Pawnikar
2. Brenda S Magenheimer
3. Keya Joshi
4. Ericka Nevarez-Munoz
5. Allan Haldane
6. Robin L Maser
7. Yinglong Miao

• Curated by eLife

  eLife assessment

  This joint computational/experimental study demonstrates the ability of synthetic peptides derived from the stalk-tethered agonist in Polycystin-1 (PC1) to re-activate signaling by a stalkless C-terminal fragment of PC1. The study is valuable as it discovered peptide agonists for PC1 and the integrated in vitro and in silico approach is potentially applicable to the analysis of related systems. Following the revision, the line of evidence presented in the current manuscript is considered convincing.

Reviewed by eLife