Biochemistry

The neuronal calcium sensor NCS-1 regulates the phosphorylation state and activity of the Gα chaperone and GEF Ric-8A

1. Daniel Muñoz-Reyes
2. Levi J McClelland
3. Sandra Arroyo-Urea
4. Sonia Sánchez-Yepes
5. Juan Sabín
6. Sara Pérez-Suárez
7. Margarita Menendez
8. Alicia Mansilla
9. Javier García-Nafría
10. Stephen Sprang
11. Maria Jose Sanchez-Barrena

• Curated by eLife

  eLife assessment

  This important study reports biochemical and structural experiments that were carried out to determine the molecular basis of calcium-sensitive regulation of the guanine exchange factor Ric8A by the neuronal calcium sensor 1 (NCS-1). Structural and biochemical evidence for the NCS-1/Ric8A interface is convincing, but evidence for the full-length interactions is incomplete due to the low resolution of cryo-EM maps. This work will have important implications for scientists interested in G-protein signaling and molecular interactions that contribute to synapse function.

Reviewed by eLife

Structural rather than catalytic role for mitochondrial respiratory chain supercomplexes

1. Michele Brischigliaro
2. Alfredo Cabrera-Orefice
3. Susanne Arnold
4. Carlo Viscomi
5. Massimo Zeviani
6. Erika Fernández-Vizarra

• Curated by eLife

  eLife assessment

  This study presents valuable findings on the organization of respiratory chain complexes in mitochondria. It provides solid evidence that respiratory supercomplex formation in the fruit fly does not impact respiratory function, suggesting the role of these complexes is structural, rather than catalytic. However, whether the conclusions extend to other species requires further evidence. This manuscript will be of broad interest to the field of mitochondrial bioenergetics.

Reviewed by eLife

An unconventional gatekeeper mutation sensitizes inositol hexakisphosphate kinases to an allosteric inhibitor

1. Tim Aguirre
2. Gillian L Dornan
3. Sarah Hostachy
4. Martin Neuenschwander
5. Carola Seyffarth
6. Volker Haucke
7. Anja Schütz
8. Jens Peter von Kries
9. Dorothea Fiedler

• Curated by eLife

  eLife assessment

  This manuscript describes a fundamental strategy for developing isozyme-selective inhibitors of inositol hexakisphosphate kinases. The compelling evidence that subtle changes to the gatekeeper position can sensitize the inositol hexakisphosphate kinase mutant to allosteric inhibitors will undoubtedly inspire other analog-sensitive inhibitor studies. This manuscript will be of interest to researchers focusing on kinase regulation and inhibitor design.

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Oligomerization-dependent and synergistic regulation of Cdc42 GTPase cycling by a GEF and a GAP

1. Sophie Tschirpke
2. Werner K-G. Daalman
3. Frank van Opstal
4. Liedewij Laan

Reviewed by Review Commons

MEMO1 binds iron and modulates iron homeostasis in cancer cells

1. Natalia Dolgova
2. Eva-Maria E Uhlemann
3. Michal T Boniecki
4. Frederick S Vizeacoumar
5. Anjuman Ara
6. Paria Nouri
7. Martina Ralle
8. Marco Tonelli
9. Syed A Abbas
10. Jaala Patry
11. Hussain Elhasasna
12. Andrew Freywald
13. Franco J Vizeacoumar
14. Oleg Y Dmitriev

• Curated by eLife

  eLife assessment

  Dolgova et al present a well-written and important manuscript focused on the mechanism of MEMO1 function in tumor cells. The authors explore whether the mechanism of MEMO1 overexpression in breast cancer, especially TNBC, is related to regulating iron given evidence that MEMO1 binds multiple proteins in the iron regulation pathway. While the data is in part compelling, the claims are based on indirect evidence for a central role of MEMO1 in tumorogenesis and perhaps metastasis via its effect on iron homeostasis.

Reviewed by eLife

Hepatic conversion of acetyl-CoA to acetate plays crucial roles in energy stress

1. Jinyang Wang
2. Yaxin Wen
3. Wentao Zhao
4. Yan Zhang
5. Furong Lin
6. Cong Ouyang
7. Huihui Wang
8. Lizheng Yao
9. Huanhuan Ma
10. Yue Zhuo
11. Huiying Huang
12. Xiulin Shi
13. Liubin Feng
14. Donghai Lin
15. Bin Jiang
16. Qinxi Li

• Curated by eLife

  eLife assessment

  This is important work that examines hepatic acetate production via ACOT12/18 in starvation and diabetes. The investigators use solid loss of function strategies in cells, including mouse primary hepatocytes, and in vivo mouse experiments to show that ACOTs are necessary for normal acetate production in the context of fasting and type 1 diabetes. Given that acetate is commonly thought to primarily represent a fermentation product, this study is of interest as it describes hepatic pathways converting fatty acids to acetate.

Reviewed by eLife

Structural basis for the phase separation of the chromosome passenger complex

1. Nikaela W Bryan
2. Aamir Ali
3. Ewa Niedzialkowska
4. Leland Mayne
5. P Todd Stukenberg
6. Ben E Black

Reviewed by Review Commons

The protective function of an immunity protein against the cis -toxic effects of a Xanthomonas Type IV Secretion System Effector

1. Gabriel U. Oka
2. Diorge P. Souza
3. Germán G. Sgro
4. Cristiane R. Guzzo
5. German Dunger
6. Chuck S. Farah

Reviewed by Review Commons

The Calpain-7 protease functions together with the ESCRT-III protein IST1 within the midbody to regulate the timing and completion of abscission

1. Elliott L Paine
2. Jack J Skalicky
3. Frank G Whitby
4. Douglas R Mackay
5. Katharine S Ullman
6. Christopher P Hill
7. Wesley I Sundquist

• Curated by eLife

  eLife assessment

  The manuscript by Paine and coworkers provides a fundamental improvement on how the enzymatic activity of CALPAIN7 (a Cys protease) influences cytokinesis mediated by the ESCRT (endosomal sorting complexes required for transport) pathway. The authors provide a convincing molecular and cellular basis for one of the several key steps involved in membrane fission during the separation of dividing eukaryotic cells. These findings should be of interest to a wide scientific audience including biochemists, structural biologists, and cell biologists.

Reviewed by eLife

Statin-mediated reduction in mitochondrial cholesterol primes an anti-inflammatory response in macrophages by upregulating Jmjd3

1. Zeina Salloum
2. Kristin Dauner
3. Yun-feng Li
4. Neha Verma
5. David Valdivieso-González
6. Víctor Almendro-Vedia
7. John D Zhang
8. Kiran Nakka
9. Mei Xi Chen
10. Jeffrey McDonald
11. Chase D Corley
12. Alexander Sorisky
13. Bao-Liang Song
14. Iván López-Montero
15. Jie Luo
16. Jeffrey F Dilworth
17. Xiaohui Zha

• Curated by eLife

  eLife assessment

  The manuscript by Salloum and colleagues shows that cholesterol-lowering statins can reduce mitochondrial cholesterol and impact epigenetic programs in macrophages. The findings could be valuable for understanding statin-mediated anti-inflammatory functions in macrophages. The major claims describing new mechanisms by which statins may regulate macrophage function via epigenetic programming are partially supported by the data presented.

Reviewed by eLife