eLife最新文献_第8页

Analysis of fast calcium dynamics of honey bee olfactory coding. 蜜蜂嗅觉编码的快速钙动态分析

IF 6.4 1区生物学

eLife Pub Date : 2024-09-05 DOI: 10.7554/eLife.93789

Marco Paoli, Antoine Wystrach, Brice Ronsin, Martin Giurfa

{"title":"Analysis of fast calcium dynamics of honey bee olfactory coding.","authors":"Marco Paoli, Antoine Wystrach, Brice Ronsin, Martin Giurfa","doi":"10.7554/eLife.93789","DOIUrl":"10.7554/eLife.93789","url":null,"abstract":"Odour processing exhibits multiple parallels between vertebrate and invertebrate olfactory systems. Insects, in particular, have emerged as relevant models for olfactory studies because of the tractability of their olfactory circuits. Here, we used fast calcium imaging to track the activity of projection neurons in the honey bee antennal lobe (AL) during olfactory stimulation at high temporal resolution. We observed a heterogeneity of response profiles and an abundance of inhibitory activities, resulting in various response latencies and stimulus-specific post-odour neural signatures. Recorded calcium signals were fed to a mushroom body (MB) model constructed implementing the fundamental features of connectivity between olfactory projection neurons, Kenyon cells (KC), and MB output neurons (MBON). The model accounts for the increase of odorant discrimination in the MB compared to the AL and reveals the recruitment of two distinct KC populations that represent odorants and their aftersmell as two separate but temporally coherent neural objects. Finally, we showed that the learning-induced modulation of KC-to-MBON synapses can explain both the variations in associative learning scores across different conditioning protocols used in bees and the bees' response latency. Thus, it provides a simple explanation of how the time contingency between the stimulus and the reward can be encoded without the need for time tracking. This study broadens our understanding of olfactory coding and learning in honey bees. It demonstrates that a model based on simple MB connectivity rules and fed with real physiological data can explain fundamental aspects of odour processing and associative learning.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of fast calcium dynamics of honey bee olfactory coding 蜜蜂嗅觉编码的快速钙动力学分析

IF 7.7 1区生物学

eLife Pub Date : 2024-09-05 DOI: https://doi.org/10.7554/elife.93789.3

Marco Paoli, Antoine Wystrach, Brice Ronsin, Martin Giurfa

{"title":"Analysis of fast calcium dynamics of honey bee olfactory coding","authors":"Marco Paoli, Antoine Wystrach, Brice Ronsin, Martin Giurfa","doi":"https://doi.org/10.7554/elife.93789.3","DOIUrl":"https://doi.org/https://doi.org/10.7554/elife.93789.3","url":null,"abstract":"Odour processing exhibits multiple parallels between vertebrate and invertebrate olfactory systems. Insects, in particular, have emerged as relevant models for olfactory studies because of the tractability of their olfactory circuits. Here, we used fast calcium imaging to track the activity of projection neurons in the honey bee antennal lobe (AL) during olfactory stimulation at high temporal resolution. We observed a heterogeneity of response profiles and an abundance of inhibitory activities, resulting in various response latencies and stimulus-specific post-odour neural signatures. Recorded calcium signals were fed to a mushroom body (MB) model constructed implementing the fundamental features of connectivity between olfactory projection neurons, Kenyon cells (KC), and MB output neurons (MBON). The model accounts for the increase of odorant discrimination in the MB compared to the AL and reveals the recruitment of two distinct KC populations that represent odorants and their aftersmell as two separate but temporally coherent neural objects. Finally, we showed that the learning-induced modulation of KC-to-MBON synapses can explain both the variations in associative learning scores across different conditioning protocols used in bees and the bees' response latency. Thus, it provides a simple explanation of how the time contingency between the stimulus and the reward can be encoded without the need for time tracking. This study broadens our understanding of olfactory coding and learning in honey bees. It demonstrates that a model based on simple MB connectivity rules and fed with real physiological data can explain fundamental aspects of odour processing and associative learning.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Asymmetric distribution of color-opponent response types across mouse visual cortex supports superior color vision in the sky 小鼠视觉皮层中颜色对立反应类型的非对称分布支持天空中的卓越色觉

IF 7.7 1区生物学

eLife Pub Date : 2024-09-05 DOI: https://doi.org/10.7554/elife.89996.4

Katrin Franke, Chenchen Cai, Kayla Ponder, Jiakun Fu, Sacha Sokoloski, Philipp Berens, Andreas Savas Tolias

{"title":"Asymmetric distribution of color-opponent response types across mouse visual cortex supports superior color vision in the sky","authors":"Katrin Franke, Chenchen Cai, Kayla Ponder, Jiakun Fu, Sacha Sokoloski, Philipp Berens, Andreas Savas Tolias","doi":"https://doi.org/10.7554/elife.89996.4","DOIUrl":"https://doi.org/https://doi.org/10.7554/elife.89996.4","url":null,"abstract":"Color is an important visual feature that informs behavior, and the retinal basis for color vision has been studied across various vertebrate species. While many studies have investigated how color information is processed in visual brain areas of primate species, we have limited understanding of how it is organized beyond the retina in other species, including most dichromatic mammals. In this study, we systematically characterized how color is represented in the primary visual cortex (V1) of mice. Using large-scale neuronal recordings and a luminance and color noise stimulus, we found that more than a third of neurons in mouse V1 are color-opponent in their receptive field center, while the receptive field surround predominantly captures luminance contrast. Furthermore, we found that color-opponency is especially pronounced in posterior V1 that encodes the sky, matching the statistics of natural scenes experienced by mice. Using unsupervised clustering, we demonstrate that the asymmetry in color representations across cortex can be explained by an uneven distribution of green-On/UV-Off color-opponent response types that are represented in the upper visual field. Finally, a simple model with natural scene-inspired parametric stimuli shows that green-On/UV-Off color-opponent response types may enhance the detection of ‘predatory’-like dark UV-objects in noisy daylight scenes. The results from this study highlight the relevance of color processing in the mouse visual system and contribute to our understanding of how color information is organized in the visual hierarchy across species.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of novel myelodysplastic syndromes prognostic subgroups by integration of inflammation, cell-type composition, and immune signatures in the bone marrow 通过整合骨髓中的炎症、细胞类型组成和免疫特征识别新型骨髓增生异常综合征预后亚组

IF 7.7 1区生物学

eLife Pub Date : 2024-09-05 DOI: https://doi.org/10.7554/elife.97096.3

Sila Gerlevik, Nogayhan Seymen, Shan Hama, Warisha Mumtaz, I Richard Thompson, Seyed R Jalili, Deniz E Kaya, Alfredo Iacoangeli, Andrea Pellagatti, Jacqueline Boultwood, Giorgio Napolitani, Ghulam J Mufti, Mohammad M Karimi

{"title":"Identification of novel myelodysplastic syndromes prognostic subgroups by integration of inflammation, cell-type composition, and immune signatures in the bone marrow","authors":"Sila Gerlevik, Nogayhan Seymen, Shan Hama, Warisha Mumtaz, I Richard Thompson, Seyed R Jalili, Deniz E Kaya, Alfredo Iacoangeli, Andrea Pellagatti, Jacqueline Boultwood, Giorgio Napolitani, Ghulam J Mufti, Mohammad M Karimi","doi":"https://doi.org/10.7554/elife.97096.3","DOIUrl":"https://doi.org/https://doi.org/10.7554/elife.97096.3","url":null,"abstract":"Mutational profiles of myelodysplastic syndromes (MDS) have established that a relatively small number of genetic aberrations, including SF3B1 and SRSF2 spliceosome mutations, lead to specific phenotypes and prognostic subgrouping. We performed a multi-omics factor analysis (MOFA) on two published MDS cohorts of bone marrow mononuclear cells (BMMNCs) and CD34 + cells with three data modalities (clinical, genotype, and transcriptomics). Seven different views, including immune profile, inflammation/aging, retrotransposon (RTE) expression, and cell-type composition, were derived from these modalities to identify the latent factors with significant impact on MDS prognosis. SF3B1 was the only mutation among 13 mutations in the BMMNC cohort, indicating a significant association with high inflammation. This trend was also observed to a lesser extent in the CD34 + cohort. Interestingly, the MOFA factor representing the inflammation shows a good prognosis for MDS patients with high inflammation. In contrast, SRSF2 mutant cases show a granulocyte-monocyte progenitor (GMP) pattern and high levels of senescence, immunosenescence, and malignant myeloid cells, consistent with their poor prognosis. Furthermore, MOFA identified RTE expression as a risk factor for MDS. This work elucidates the efficacy of our integrative approach to assess the MDS risk that goes beyond all the scoring systems described thus far for MDS.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A robust brain network for sustained attention from adolescence to adulthood that predicts later substance use 从青春期到成年期，持续注意力的强大大脑网络可预测日后的药物使用情况

IF 7.7 1区生物学

eLife Pub Date : 2024-09-05 DOI: https://doi.org/10.7554/elife.97150.3

Yihe Weng, Johann Kruschwitz, Laura M Rueda-Delgado, Kathy L Ruddy, Rory Boyle, Luisa Franzen, Emin Serin, Tochukwu Nweze, Jamie Hanson, Alannah Smyth, Tom Farnan, Tobias Banaschewski, Arun LW Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny A Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Jane McGrath, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomas Paus, Luise Poustka, Nathalie Holz, Juliane Fröhner, Michael N Smolka, Nilakshi Vaidya, Gunter Schumann, Henrik Walter, Robert Whelan, IMAGEN Consortium

{"title":"A robust brain network for sustained attention from adolescence to adulthood that predicts later substance use","authors":"Yihe Weng, Johann Kruschwitz, Laura M Rueda-Delgado, Kathy L Ruddy, Rory Boyle, Luisa Franzen, Emin Serin, Tochukwu Nweze, Jamie Hanson, Alannah Smyth, Tom Farnan, Tobias Banaschewski, Arun LW Bokde, Sylvane Desrivières, Herta Flor, Antoine Grigis, Hugh Garavan, Penny A Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Jane McGrath, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomas Paus, Luise Poustka, Nathalie Holz, Juliane Fröhner, Michael N Smolka, Nilakshi Vaidya, Gunter Schumann, Henrik Walter, Robert Whelan, IMAGEN Consortium","doi":"https://doi.org/10.7554/elife.97150.3","DOIUrl":"https://doi.org/https://doi.org/10.7554/elife.97150.3","url":null,"abstract":"Substance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under-powered and could not indicate if impairment in sustained attention was a predictor of substance use or a marker of the inclination to engage in such behavior. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1000 participants. Behaviors and brain connectivity associated with diminished sustained attention at age 14 predicted subsequent increases in cannabis and cigarette smoking, establishing sustained attention as a robust biomarker for vulnerability to substance use. Individual differences in network strength relevant to sustained attention were preserved across developmental stages and sustained attention networks generalized to participants in an external dataset. In summary, brain networks of sustained attention are robust, consistent, and able to predict aspects of later substance use.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

White matter structural bases for phase accuracy during tapping synchronization. 敲击同步过程中相位准确性的白质结构基础

IF 6.4 1区生物学

eLife Pub Date : 2024-09-04 DOI: 10.7554/eLife.83838

Pamela Garcia-Saldivar, Cynthia de León, Felipe A Mendez Salcido, Luis Concha, Hugo Merchant

{"title":"White matter structural bases for phase accuracy during tapping synchronization.","authors":"Pamela Garcia-Saldivar, Cynthia de León, Felipe A Mendez Salcido, Luis Concha, Hugo Merchant","doi":"10.7554/eLife.83838","DOIUrl":"https://doi.org/10.7554/eLife.83838","url":null,"abstract":"We determined the intersubject association between the rhythmic entrainment abilities of human subjects during a synchronization-continuation tapping task (SCT) and the macro- and microstructural properties of their superficial (SWM) and deep (DWM) white matter. Diffusion-weighted images were obtained from 32 subjects who performed the SCT with auditory or visual metronomes and five tempos ranging from 550 to 950 ms. We developed a method to determine the density of short-range fibers that run underneath the cortical mantle, interconnecting nearby cortical regions (U-fibers). Notably, individual differences in the density of U-fibers in the right audiomotor system were correlated with the degree of phase accuracy between the stimuli and taps across subjects. These correlations were specific to the synchronization epoch with auditory metronomes and tempos around 1.5 Hz. In addition, a significant association was found between phase accuracy and the density and bundle diameter of the corpus callosum, forming an interval-selective map where short and long intervals were behaviorally correlated with the anterior and posterior portions of the corpus callosum. These findings suggest that the structural properties of the SWM and DWM in the audiomotor system support the tapping synchronization abilities of subjects, as cortical U-fiber density is linked to the preferred tapping tempo and the bundle properties of the corpus callosum define an interval-selective topography.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantitative mapping of proteasome interactomes and substrates using ProteasomeID 利用蛋白酶体标识（ProteasomeID）定量绘制蛋白酶体相互作用组和底物图谱

IF 7.7 1区生物学

eLife Pub Date : 2024-09-04 DOI: https://doi.org/10.7554/elife.93256.3

Aleksandar Bartolome, Julia C Heiby, Domenico Di Fraia, Ivonne Heinze, Hannah Knaudt, Ellen Spaeth, Omid Omrani, Alberto Minetti, Maleen Hofmann, Joanna M Kirkpatrick, Therese Dau, Alessandro Ori

引用次数: 0

White matter structural bases for phase accuracy during tapping synchronization 敲击同步过程中相位准确性的白质结构基础

IF 7.7 1区生物学

eLife Pub Date : 2024-09-04 DOI: https://doi.org/10.7554/elife.83838

Pamela Garcia-Saldivar, Cynthia de León, Felipe A Mendez Salcido, Luis Concha, Hugo Merchant

{"title":"White matter structural bases for phase accuracy during tapping synchronization","authors":"Pamela Garcia-Saldivar, Cynthia de León, Felipe A Mendez Salcido, Luis Concha, Hugo Merchant","doi":"https://doi.org/10.7554/elife.83838","DOIUrl":"https://doi.org/https://doi.org/10.7554/elife.83838","url":null,"abstract":"We determined the intersubject association between the rhythmic entrainment abilities of human subjects during a synchronization-continuation tapping task (SCT) and the macro- and microstructural properties of their superficial (SWM) and deep (DWM) white matter. Diffusion-weighted images were obtained from 32 subjects who performed the SCT with auditory or visual metronomes and five tempos ranging from 550 to 950 ms. We developed a method to determine the density of short-range fibers that run underneath the cortical mantle, interconnecting nearby cortical regions (U-fibers). Notably, individual differences in the density of U-fibers in the right audiomotor system were correlated with the degree of phase accuracy between the stimuli and taps across subjects. These correlations were specific to the synchronization epoch with auditory metronomes and tempos around 1.5 Hz. In addition, a significant association was found between phase accuracy and the density and bundle diameter of the corpus callosum, forming an interval-selective map where short and long intervals were behaviorally correlated with the anterior and posterior portions of the corpus callosum. These findings suggest that the structural properties of the SWM and DWM in the audiomotor system support the tapping synchronization abilities of subjects, as cortical U-fiber density is linked to the preferred tapping tempo and the bundle properties of the corpus callosum define an interval-selective topography.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Quantitative mapping of proteasome interactomes and substrates using ProteasomeID. 使用 ProteasomeID 对蛋白酶体相互作用组和底物进行定量制图。

IF 6.4 1区生物学

eLife Pub Date : 2024-09-04 DOI: 10.7554/eLife.93256

Aleksandar Bartolome, Julia C Heiby, Domenico Di Fraia, Ivonne Heinze, Hannah Knaudt, Ellen Spaeth, Omid Omrani, Alberto Minetti, Maleen Hofmann, Joanna M Kirkpatrick, Therese Dau, Alessandro Ori

{"title":"Quantitative mapping of proteasome interactomes and substrates using ProteasomeID.","authors":"Aleksandar Bartolome, Julia C Heiby, Domenico Di Fraia, Ivonne Heinze, Hannah Knaudt, Ellen Spaeth, Omid Omrani, Alberto Minetti, Maleen Hofmann, Joanna M Kirkpatrick, Therese Dau, Alessandro Ori","doi":"10.7554/eLife.93256","DOIUrl":"10.7554/eLife.93256","url":null,"abstract":"Proteasomes are essential molecular machines responsible for the degradation of proteins in eukaryotic cells. Altered proteasome activity has been linked to neurodegeneration, auto-immune disorders and cancer. Despite the relevance for human disease and drug development, no method currently exists to monitor proteasome composition and interactions in vivo in animal models. To fill this gap, we developed a strategy based on tagging of proteasomes with promiscuous biotin ligases and generated a new mouse model enabling the quantification of proteasome interactions by mass spectrometry. We show that biotin ligases can be incorporated in fully assembled proteasomes without negative impact on their activity. We demonstrate the utility of our method by identifying novel proteasome-interacting proteins, charting interactomes across mouse organs, and showing that proximity-labeling enables the identification of both endogenous and small-molecule-induced proteasome substrates.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":6.4,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11374303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A 2-hydroxybutyrate-mediated feedback loop regulates muscular fatigue 2- 羟基丁酸介导的反馈回路调节肌肉疲劳

IF 7.7 1区生物学

eLife Pub Date : 2024-09-03 DOI: https://doi.org/10.7554/elife.92707.2

Brennan J Wadsworth, Marina Leiwe, Eleanor A Minogue, Pedro P Cunha, Viktor Engman, Carolin Brombach, Christos Asvestis, Shiv K Sah-Teli, Emilia Marklund, Peppi Karppinen, Jorge L Ruas, Helene Rundqvist, Johanna T Lanner, Randall S Johnson

{"title":"A 2-hydroxybutyrate-mediated feedback loop regulates muscular fatigue","authors":"Brennan J Wadsworth, Marina Leiwe, Eleanor A Minogue, Pedro P Cunha, Viktor Engman, Carolin Brombach, Christos Asvestis, Shiv K Sah-Teli, Emilia Marklund, Peppi Karppinen, Jorge L Ruas, Helene Rundqvist, Johanna T Lanner, Randall S Johnson","doi":"https://doi.org/10.7554/elife.92707.2","DOIUrl":"https://doi.org/https://doi.org/10.7554/elife.92707.2","url":null,"abstract":"Several metabolites have been shown to have independent and at times unexpected biological effects outside of their metabolic pathways. These include succinate, lactate, fumarate, and 2-hydroxyglutarate. 2-Hydroxybutyrate (2HB) is a byproduct of endogenous cysteine synthesis, produced during periods of cellular stress. 2HB rises acutely after exercise; it also rises during infection and is also chronically increased in a number of metabolic disorders. We show here that 2HB inhibits branched-chain aminotransferase enzymes, which in turn triggers a SIRT4-dependent shift in the compartmental abundance of protein ADP-ribosylation. The 2HB-induced decrease in nuclear protein ADP-ribosylation leads to a C/EBPβ-mediated transcriptional response in the branched-chain amino acid degradation pathway. This response to 2HB exposure leads to an improved oxidative capacity in vitro. We found that repeated injection with 2HB can replicate the improvement to oxidative capacity that occurs following exercise training. Together, we show that 2-HB regulates fundamental aspects of skeletal muscle metabolism.","PeriodicalId":11640,"journal":{"name":"eLife","volume":null,"pages":null},"PeriodicalIF":7.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0