Biochemistry

ᴅ-serine suppresses one-carbon metabolism by competing with mitochondrial ʟ-serine transport

1. Masataka Suzuki
2. Kenichiro Adachi
3. Pattama Wiriyasermukul
4. Mariko Fukumura
5. Ryota Tamura
6. Yoshinori Hirano
7. Yumi Aizawa
8. Tetsuya Miyamoto
9. Sakiko Taniguchi
10. Masahiro Toda
11. Hiroshi Homma
12. Kohsuke Kanekura
13. Kenji Yasuoka
14. Takanori Kanai
15. Masahiro Sugimoto
16. Shushi Nagamori
17. Masato Yasui
18. Jumpei Sasabe

• Curated by eLife

  eLife Assessment

  This work presents valuable new data on the role of D-Serine and how it competes with its stereoisomer L-Serine to influence metabolism. The work presents a variety of convincing experimental data combined with simulated results to investigate the mechanisms focused on one-carbon metabolism, which is relevant for several research fields. However, some claims are only partially supported by data, and critical areas comparing L- vs D-Serine and further mechanistic studies are required. Furthermore, while the work has potential for various fields, the work has only been studied in a limited cell type and context.

Reviewed by eLife

A Membrane-Disruptive Action of VBIT-4 Challenges Its Role as a Widely Used VDAC1 Oligomerization Inhibitor

1. Varun Ravishankar
2. Luís Borges-Araújo
3. Megha Rajendran
4. Elodie Lafargue
5. Deborah Byrne
6. Nicolas Buzhinsky
7. Mya S Wolfe
8. Wendy Fitzgerald
9. Nina A Bautista
10. Bethel G Beyene
11. Motahareh G Larimi
12. Jean-Pierre Duneau
13. James Sturgis
14. Sergey M Bezrukov
15. Ignacio Casuso
16. Tatiana Rostovtseva
17. Lucie Bergdoll

• Curated by eLife

  eLife Assessment

  This work provides a reassessment of VBIT-4, a compound previously proposed to inhibit oligomerization of the crucial protein known as the mitochondrial voltage-dependent anion channel. Combining complementary experimental approaches with molecular dynamics simulations, the authors provide compelling evidence that VBIT-4 primarily disrupts lipid membranes and induces channel-independent cytotoxicity. The study has important implications for interpreting previous work using VBIT-4 as a probe of channel function and highlights the need to consider membrane-disruptive effects when evaluating drug mechanisms.

Reviewed by eLife

Profiling of terminating ribosomes reveals translational control at stop codons

1. Longfei Jia
2. Yuanhui Mao
3. Saori Uematsu
4. Xinyi Ashley Liu
5. Leiming Dong
6. Leonardo Henrique França de Lima
7. Shu-Bing Qian

• Curated by eLife

  eLife Assessment

  This manuscript reports on the application of ribosome profiling (EZRA-seq and eRF1-seq) and massively parallel reporter assays (MPRA) to identify and characterize sequence elements that regulate translation termination. The authors conclude that a GA-rich element upstream of stop codons is associated with ribosome pausing during translation termination; in contrast, C-rich sequences upstream of stop codons abolish termination pausing. While the overall findings of this study are useful and the identification of GA-rich elements upstream of stop codons is compelling, support for several other claims remains incomplete. Specifically, the evidence that the MPRA results mirror the ribosome profiling, that a C-rich sequence preceding the stop codon promotes termination slippage in cellular mRNAs, and that Rps26 interferes with mRNA interactions to regulate translation termination would benefit from further support.

Reviewed by eLife

The chromokinesin Kid (KIF22) forms a homodimer, moves processively along microtubules and transports double-stranded DNA

1. Shinsuke Niwa
2. Natsuki Furusaki
3. Tomoki Kita
4. Yuki Suzuki
5. Kyoko Chiba

• Curated by eLife

  eLife Assessment

  This important study clarifies the mechanism by which the kinesin-10 motor protein, chromosome-associated kinesin, Kid (KIF22), enables chromosome movement during mitosis, demonstrating that human and Xenopus Kid proteins function as processive, homodimeric kinesins capable of processive microtubule plus-end motility. The convincing work highlights that Kid can recruit and transport duplex DNA along microtubules via its conserved C-terminal DNA binding domain, revising our understanding of chromokinesins' role in chromosome motility during mitosis. It will be of interest to those in the molecule motor community working at the molecular, cellular, and organismal levels.

Reviewed by eLife

Cardiolipin deficiency disrupts electron transport chain and drives steatohepatitis

1. Marisa J Brothwell
2. Guoshen Cao
3. J Alan Maschek
4. Annelise M Poss
5. Alek D Peterlin
6. Liping Wang
7. Talia B Baker
8. Justin L Shahtout
9. Piyarat Siripoksup
10. Quentinn J Pearce
11. Jordan M Johnson
12. Fabian M Finger
13. Alexandre Prola
14. Sarah A Pellizzari
15. Gillian L Hale
16. Allison M Manuel
17. Shinya Watanabe
18. Edwin R Miranda
19. Kajsa E Affolter
20. Trevor S Tippetts
21. Linda S Nikolova
22. Ran Hee Choi
23. Stephen T Decker
24. Mallikarjun Patil
25. J Leon Catrow
26. William L Holland
27. Sara M Nowinski
28. Daniel S Lark
29. Kelsey H Fisher-Wellman
30. Patrice N Mimche
31. Kimberley J Evason
32. James E Cox
33. Scott A Summers
34. Zach Gerhart-Hines
35. Katsuhiko Funai

• Curated by eLife

  eLife Assessment

  This revised manuscript retreats from the original claim of establishing a causal link between cardiolipin deficiency and the progression from steatotic liver disease to steatohepatitis and instead advances a more limited mechanistic conclusion: that cardiolipin deficiency perturbs electron transport and promotes electron leak from the mitochondrial respiratory chain. The experimental evidence supporting this revised claim is now solid, and the potential for increased electron leak to contribute to liver pathophysiology is demonstrated. However, absent evidence that cardiolipin deficiency is causally upstream of disease progression, the overall significance of the work remains limited. While the study provides a convincing analysis of mitochondrial bioenergetics, the narrowing of its central claim diminishes its impact relative to that proposed in the original submission.

Reviewed by eLife

Dynamic assembly of malate dehydrogenase–citrate synthase multienzyme complex in the mitochondria

1. Joy Omini
2. Inga Krassovskaya
3. Taiwo Adeolu Dele-Osibanjo
4. Connor Pedersen
5. Toshihiro Obata

• Curated by eLife

  eLife Assessment

  This important study provides novel information on multi-enzyme complexes, known as metabolons, that form between sequential enzymes in a metabolic pathway. Using an innovative NanoBiT split-luciferase system, the authors present compelling evidence that malate dehydrogenase (MDH1) and citrate synthase (CIT1) dynamically associate under different metabolic conditions in Saccharomyces cerevisiae. The findings suggest the dynamic MDH1-CIT1 interaction facilitates control of TCA pathway flux rate.

Reviewed by eLife

Single-step in vitro reconstitution of the Escherichia coli ribosome mediated by two GTPase factors, EngA and ObgE

1. Aya Sato
2. Weng Yu Lai
3. Yusuke Sakai
4. Keiko Masuda
5. Yoshihiro Shimizu

• Curated by eLife

  eLife Assessment

  This is a valuable study presenting convincing data indicating that the bacterial GTPases EngA and ObgE enable single-step reconstitution of functional 50S ribosomal subunits under near-physiological conditions. The study elegantly bridges the gap between the non-physiological aspects of the previous two-step reconstitution method and the extract-dependent iSAT system to enable assembly of highly functional ribosomes under translation-compatible conditions. The reported findings represent substantial progress towards achieving a bottom-up reconstruction of the translation machinery from synthetic parts.

Reviewed by eLife

Integrating computational protein structure predictions and genetic dependencies yields an atlas of human multi-protein complexes (AHMPC)

1. Michael Uckelmann
2. Daniel Alvarez Salmoral
3. Carmen Maiella
4. Onno Bleijerveld
5. Ceri Zwart
6. Eric Marcus
7. Joren Brunekreef
8. Jonas Teuwen
9. Roderick Beijersbergen
10. Anastassis Perrakis

Reviewed by Review Commons