Physiology

The titin N2A-MARP signalosome constrains muscle longitudinal hypertrophy in response to stretch

1. Robbert van der Pijl
2. Jochen Gohlke
3. Joshua Strom
4. Eva Peters
5. Shengyi Shen
6. Stefan Conijn
7. Zaynab Hourani
8. Stephan Lange
9. Ju Chen
10. Paul Langlais
11. Siegfried Labeit
12. Henk Granzier
13. Coen Ottenheijm

• Curated by eLife

  eLife Assessment

  The work by van der Pijl presents important findings on the role of titin-associated muscle ankyrin repeat proteins (MARPs) on hypertrophy via mTOR signalling. The study presents rigourous data using in vivo loss-of-function and pharmacological approaches to investigate effects on hypertrophy. While the evidence supporting the role of MARPs on hypertrophy is solid, there are limitations. For example, the use of Rapamycin only inhibits some aspects of mTORC1 signalling and the study is limited to analysis of the diaphragm and thus it is not clear if the mechanisms are conserved across other muscle types.

Reviewed by eLife

Orco regulates the circadian activity of pheromone-sensitive olfactory receptor neurons in hawkmoths

1. Aditi Vijayan
2. Mauro Forlino
3. Yajun Chang
4. Pablo Rojas
5. Katrin Schröder
6. Anna C Schneider
7. Martin E Garcia
8. Monika Stengl

• Curated by eLife

  eLife Assessment

  This valuable study uses technically compelling long-term in vivo recordings and computational modeling to investigate whether hawkmoth olfactory receptor neurons show circadian modulation of spontaneous firing. The authors further propose the provocative model that post-translational mechanisms, rather than the transcriptional-translational processes, may contribute to circadian regulation of neuronal excitability. However, the evidence for circadian firing in these neurons, and for post-translational modification of Orco as the underlying mechanism, remains incomplete. In contrast, the study does provide strong evidence that the application of cyclic nucleotides can modulate Orco-dependent activity at a single time point, and reports that the temporal pattern of Orco transcript abundance is not circadian.

Reviewed by eLife

Exercise-Induced Hypoalgesia Following High- vs. Low-Intensity Aerobic Exercise in Fit Females

1. Janne I Nold
2. Tahmine Fadai
3. Zora P Gerbers
4. Christian Büchel

• Curated by eLife

  eLife Assessment

  This study proposes that fitness level influences exercise-induced hypoalgesia in women. However, the evidence to support this claim is incomplete: the conclusions rely on a small interaction that emerges only under specific conditions and are incongruent with the title, the findings are inconsistent across pain modalities and stimulus intensities, the analysis approach does not fully exploit the continuous pain ratings collected, and the absence of a baseline condition limits the interpretability of results as reflecting true hypoalgesia. Additionally, the methods by which fitness level was categorized across cohorts can be questioned, and the results and figures do not clearly illustrate how between-group comparisons were conducted. With a proper revision, it could be useful for sports medicine practitioners to consider how they administer exercise protocols to help those experiencing pain.

Reviewed by eLife

Thermogenic Adipose ADH5 Counteracts Age-related Metabolic Decline

1. Sara C Sebag
2. Tate Neff
3. Qingwen Qian
4. Arvand Asghari
5. Zhuozhi Wang
6. Zeyuan Zhang
7. Mark Li
8. Meihua Hao
9. Vitor A Lira
10. Hongli Sun
11. Matthew J Potthoff
12. Ling Yang

• Curated by eLife

  eLife Assessment

  This valuable study identifies a brown adipose tissue-specific heat shock factor 1 (HSF1)-alcohol dehydrogenase 5 (ADH5) axis that regulates oxidative stress and cellular senescence during aging. The authors show that ADH5 deficiency drives BAT dysfunction and contributes to organismal health decline in aged mice. The evidence is convincing, and the work will be of broad interest to the adipose tissue and aging research communities.

Reviewed by eLife

NK2R signaling governs intestinal lipid mobilization and mucosal inflammation

1. Pedro A Perez
2. Chung-Chih Liu
3. Alessandra Ferrari
4. Nicole Littlejohn
5. John Paul Kennelly
6. Emma Robinson
7. Vân TB Nguyen-Tran
8. Jon Athanacio
9. Sean B Joseph
10. Zaid Amso
11. Peter Tontonoz
12. Supriya Srinivasan

• Curated by eLife

  eLife Assessment

  This is an important study on the role of the neurokinin-2 receptor (NK2R) as a regulatory node connecting intestinal lipid metabolism, mucosal immunity, and the gut microbiome, bidirectionally regulating enterocyte lipid uptake, lipid droplet storage, chylomicron output, and systemic metabolic parameters in DIO mice. The authors present solid evidence linking Tacr2 deletion to reprogrammed epithelial lineage allocation, dampened immune gene expression, and male-biased protection from DSS colitis, despite dysbiotic microbiota. However, the causal evidence for some mechanistic and pro-inflammatory NK2R claims remains incomplete and potentially confounding, requiring additional cell-type-specific and functional experiments.

Reviewed by eLife

Differential Regulation of Hepatic Macrophage Fate by Chi3l1 in MASLD

1. Jia He
2. Bo Chen
3. Weiju Lu
4. Xiong Wang
5. Ruoxue Yang
6. Chengxiang Deng
7. Xiane Zhu
8. Keqin Wang
9. Lang Wang
10. Cheng Xie
11. Rui Li
12. Xiaokang Lu
13. Ruizhi Yang
14. Cheng Peng
15. Canpeng Li
16. Zhao Shan

• Curated by eLife

  eLife Assessment

  This study provides an insight into the role of a Chi3l1 in liver macrophages during metabolic disease. The evidence is solid with the authors now addressing most concerns, although one key conclusion is not fully supported by the data presented. Overall, the work offers a useful contribution to the field.

Reviewed by eLife

Cytokine control of systemic hypoxia tolerance in Drosophila

1. Kate Ding
2. Prajakta Bodkhe
3. Byoungchun Lee
4. Danielle Polan
5. Amy Wycislik
6. Tiffany Cheung
7. Sophie Wu
8. Savraj S Grewal

Reviewed by Review Commons, PREreview

Zinc is a Key Regulator of the Sperm-Specific K+ Channel (Slo3) Function

1. Rizki Tsari Andriani
2. Tanadet Pipatpolkai
3. Haruhiko Miyata
4. Masahito Ikawa
5. Yasushi Okamura
6. Takafumi Kawai

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding on the role of intracellular zinc as a regulator of the sperm-specific potassium channel Slo3, demonstrating that zinc export during capacitation contributes to alkalinization-induced membrane hyperpolarization. The electrophysiological evidence supporting zinc-mediated inhibition of Slo3 is solid, though the mechanistic basis of this inhibition is not complete, as the proposed zinc-binding site involving E169 and E205 has not been directly tested through double-mutant analysis. This work will be of interest to reproductive biologists and ion channel biophysicists studying the molecular mechanisms of sperm capacitation.

Reviewed by eLife

Natural xanthones as α-Mangostin induce vasorelaxation involving key gating residues in the S6 domain of BK channels

1. Soenke Cordeiro
2. Robert Patejdl
3. Thomas Baukrowitz
4. Marianne A Musinszki

• Curated by eLife

  eLife Assessment

  The present manuscript by Cordeiro et al., shows convincing evidence that α-mangostin, a xanthone obtained from the fruit of the Garcinia mangostana tree, behaves as a strong activator of the large-conductance (BK) potassium channels. The authors suggest that α-mangostin activation of the BK channel is state-independent, and molecular docking and mutagenesis suggest that α-mangostin binds to a site in the internal cavity. Additionally, the authors show that α-mangostin can relax arteries, further suggesting the plausibility of the proposed effects of this compound. These are valuable findings that should be of interest to channel biophysicists and physiologists alike.

Reviewed by eLife

Metabolism fine tuning and cardiokines secretion represent adaptative responses of the heart to High Fat and High Sugar Diets in flies

1. Lucie Khamvongsa-Charbonnier
2. Laurent Kremmer
3. Magali Torres
4. Sallouha Krifa
5. Charis Aubert
6. Alice Corbet
7. Loïc Crespo
8. Laurence Röder
9. Laurent Perrin
10. Nathalie Arquier

Reviewed by Review Commons