Molecules and Cells最新文献

Mitochondrial calcium modulates odor-mediated behavioral plasticity in C. elegans. 线粒体钙调节秀丽隐杆线虫气味介导的行为可塑性。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-05-04 DOI: 10.1016/j.mocell.2026.100367

Hee Kyung Lee, Abe Gayle Santos, Kyu-Sang Park, Kyoung-Hye Yoon

{"title":"Mitochondrial calcium modulates odor-mediated behavioral plasticity in C. elegans.","authors":"Hee Kyung Lee, Abe Gayle Santos, Kyu-Sang Park, Kyoung-Hye Yoon","doi":"10.1016/j.mocell.2026.100367","DOIUrl":"https://doi.org/10.1016/j.mocell.2026.100367","url":null,"abstract":"<p><p>Despite growing understanding of the various roles mitochondria play in neurons, how they contribute to higher brain functions such as learning and memory remains underexplored. Here, using the nematode Caenorhabditis elegans, we found that the mitochondrial calcium uniporter (MCU) pore forming unit MCU-1 is required for aversive learning of specific odors sensed by the AWC sensory neuron. MCU-1 expression was required in the sensory neuron at the time of odor conditioning for proper behavioral response to 60 min of prolonged odor exposure. We discovered that calcium entry into the mitochondria in AWC responds to the length of odor stimulus: calcium is elevated after 60 min of odor but not after 30 min, suggesting a gating mechanism that can discriminate the duration of sensory stimuli. Through genetic and pharmacological manipulation, we show that calcium influx through the MCU causes mtROS production, leading to NLP-1 secretion from the AWC neuron, and odor learning. Overall, our results demonstrate that, by regulating mitochondrial calcium entry, mitochondria can respond to the length of a sensory stimulus to modulate the synaptic response, resulting in context-appropriate learning and behavior.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100367"},"PeriodicalIF":6.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The 40% weight-reduction craze: market volatility, metabolic nuance, and the quest for sustainable health. 40%的减肥热潮：市场波动，新陈代谢的细微差别，以及对可持续健康的追求。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-05-01 DOI: 10.1016/j.mocell.2026.100364

Weiping Han, Peter Shepherd, Kohjiro Ueki, Jia Li, Aimin Xu, Geunho Oh, Jae Bum Kim

引用次数: 0

Tandem repeats in human brain evolution and disease susceptibility. 串联重复序列在人脑进化和疾病易感性中的作用。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-04-27 DOI: 10.1016/j.mocell.2026.100363

Hyeji Lee, Joon-Yong An

{"title":"Tandem repeats in human brain evolution and disease susceptibility.","authors":"Hyeji Lee, Joon-Yong An","doi":"10.1016/j.mocell.2026.100363","DOIUrl":"https://doi.org/10.1016/j.mocell.2026.100363","url":null,"abstract":"<p><p>Tandem repeats (TRs) are dynamic genomic elements characterized by exceptionally high mutation rates, reversibility, and the capacity to generate graduated phenotypic effects. These properties enable TRs to modulate gene regulation at multiple levels-from transcription and chromatin organization to splicing and protein function. In the human lineage, TR expansions have been recurrently associated with brain evolution, with human-specific repeats enriched near neurodevelopmental genes and linked to neural-specific regulatory elements. However, this same mutational plasticity that facilitated cognitive innovation also introduced genomic instability, rendering the nervous system particularly vulnerable to repeat-associated dysfunction. The brain's unique cellular and molecular properties create an environment particularly permissive to repeat-mediated pathology. Recent studies have revealed diverse pathogenic mechanisms beyond classical models, highlighting the multifaceted ways in which repeat instability can disrupt neural function. Understanding TRs as integral components of neural regulatory architecture, rather than isolated pathogenic loci, provides a framework for interpreting the genetic basis of neurological and psychiatric disorders.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100363"},"PeriodicalIF":6.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Targeting serine metabolism boosts antimycobacterial immunity during Mycobacterium tuberculosis H37Rv Infection. 靶向丝氨酸代谢增强结核分枝杆菌H37Rv感染期间的抗细菌免疫。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-04-26 DOI: 10.1016/j.mocell.2026.100366

Sang-Hun Son, Ji-Ae Choi, Jaewhan Kim, Tam Doan Nguyen, Junghwan Lee, Doyi Son, Seoyeon Jo, Chang-Hwa Song

{"title":"Targeting serine metabolism boosts antimycobacterial immunity during Mycobacterium tuberculosis H37Rv Infection.","authors":"Sang-Hun Son, Ji-Ae Choi, Jaewhan Kim, Tam Doan Nguyen, Junghwan Lee, Doyi Son, Seoyeon Jo, Chang-Hwa Song","doi":"10.1016/j.mocell.2026.100366","DOIUrl":"https://doi.org/10.1016/j.mocell.2026.100366","url":null,"abstract":"<p><p>Serine metabolism is pivotal in regulating immune cell function and molding the host microenvironment during infection, yet its impact on antimycobacterial immunity remains elusive. Here, we probe the role of serine metabolism in Mycobacterium tuberculosis (Mtb)-infected macrophages. We reveal that Mtb infection induces enzymes associated with the serine synthesis pathway (SSP) and serine transporters. Moreover, inhibition of the key SSP enzyme or restriction of exogenous serine boosts antimycobacterial immunity in both in vitro and in vivo. Depletion of serine reduces reactive oxygen species (ROS) levels by diminishing the levels of reduced nicotinamide adenine dinucleotide. This ROS reduction destabilizes hypoxia-inducible factor 1 alpha, impairing glucose uptake and ATP production. Consequently, reduced ATP production activates AMP-activated protein kinase, which inhibits mTOR and induces autophagy, thereby exerting antimycobacterial effect. These findings underscore serine's role as a crucial immune metabolite during Mtb infection and propose that manipulating serine metabolism holds therapeutic promise against mycobacterial infections.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100366"},"PeriodicalIF":6.5,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Brain-inspired strategies for efficient artificial intelligence. 高效人工智能的大脑启发策略。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-04-24 DOI: 10.1016/j.mocell.2026.100365

Min-Seo Kim, Hyoung F Kim

{"title":"Brain-inspired strategies for efficient artificial intelligence.","authors":"Min-Seo Kim, Hyoung F Kim","doi":"10.1016/j.mocell.2026.100365","DOIUrl":"https://doi.org/10.1016/j.mocell.2026.100365","url":null,"abstract":"<p><p>Despite being constrained by a rigid skull and a fixed number of neurons, the brain excels in processing diverse information and making adaptive decisions with remarkable efficiency. This raises a central question at the intersection of neuroscience and artificial intelligence: How does the brain achieve such high performance with limited physical resources? We addressed this question by examining the anatomical funneling architecture of the basal ganglia, a central hub for value-based decision-making. Through parallel processing, distinct circuits support cognitive flexibility and habitual stability, enabling efficient allocation of neural resources and context-sensitive engagement in specialized computations. In contrast, convergent processing compresses the input across circuits, allowing the efficient extraction of core information for decision-making, a form of quantitative efficiency that minimizes the number of neurons required. However, this compression can degrade the fidelity. To address this, the brain employs qualitative efficiency in which population-level neural patterns preserve fine-grained information and support generalization across similar contexts. Finally, we propose that the cortico-basal ganglia system achieves cognitive efficiency by funneling the anatomical structure and dimensionality reduction to optimize both performance and energy demands. These principles offer a biologically grounded framework for developing brain-inspired, resource-efficient artificial intelligence (AI) systems that balance generalization with precision.</p>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":" ","pages":"100365"},"PeriodicalIF":6.5,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Caffeine extends lifespan by enhancing lysosomal lipolysis in Caenorhabditis elegans. 咖啡因通过促进秀丽隐杆线虫溶酶体的脂溶性来延长寿命。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-04-16 DOI: 10.1016/j.mocell.2026.100358

Hyemin Min, Eunseok Kang, Gee-Yoon Lee, Laura Bahr, Arjumand Ghazi, Seung-Jae V Lee

引用次数: 0

Amygdala-hippocampus circuit regulates stress coping via mGluR5-dependent BDNF signaling 杏仁核-海马回路通过mglur5依赖性BDNF信号传导调节应激应对。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-03-01 Epub Date: 2026-01-21 DOI: 10.1016/j.mocell.2026.100320

Tae-Eun Kim , Tae-Yong Choi , Ja Wook Koo , Jeongseop Kim

{"title":"Amygdala-hippocampus circuit regulates stress coping via mGluR5-dependent BDNF signaling","authors":"Tae-Eun Kim , Tae-Yong Choi , Ja Wook Koo , Jeongseop Kim","doi":"10.1016/j.mocell.2026.100320","DOIUrl":"10.1016/j.mocell.2026.100320","url":null,"abstract":"<div><div>Stress-related psychiatric disorders are underpinned by dysfunction in the prefrontal cortex and hippocampus; however, the underlying circuit-specific mechanisms remain ill-defined. Here, we identified the basolateral amygdala (BLA)-to-ventral hippocampus (vHPC) circuit as a critical regulator of stress-coping behaviors. Although chronic social defeat stress reduced the mGluR5 expression in both the vHPC and medial prefrontal cortex (mPFC), our circuit-specific behavioral analysis revealed that the activation of the BLA-vHPC circuit produced a significantly greater improvement in coping behavior compared with the activation of the BLA-mPFC circuit. Subsequently, we mechanistically demonstrated that reduced mGluR5 in the vHPC directly impairs CREB-mediated brain-derived neurotrophic factor (BDNF) transcription, a molecular cascade tightly linked to passive coping. These findings reveal a novel circuit-specific molecular mechanism governing stress recovery, positioning the mGluR5-BDNF pathway as a highly specific and promising therapeutic target for future gene therapy interventions.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"49 3","pages":"Article 100320"},"PeriodicalIF":6.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Cover and caption 封面及标题

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-03-01 Epub Date: 2026-02-26 DOI: 10.1016/S1016-8478(26)00027-0

引用次数: 0

HAP1 interaction with KCNQ4 attenuates channel surface expression and function HAP1与KCNQ4的相互作用减弱了通道表面的表达和功能。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-03-01 Epub Date: 2026-01-29 DOI: 10.1016/j.mocell.2026.100322

Jung Ah Kim , Kyung Seok Oh , Jae Won Roh , Young Ik Koh , Haiyue Lin , Jinsei Jung , Heon Yung Gee

{"title":"HAP1 interaction with KCNQ4 attenuates channel surface expression and function","authors":"Jung Ah Kim , Kyung Seok Oh , Jae Won Roh , Young Ik Koh , Haiyue Lin , Jinsei Jung , Heon Yung Gee","doi":"10.1016/j.mocell.2026.100322","DOIUrl":"10.1016/j.mocell.2026.100322","url":null,"abstract":"<div><div>The voltage–gated channel subfamily Q member 4 (KCNQ4), a K+ channel, is one of the most frequently mutated genes in autosomal dominant nonsyndromic hearing loss. KCNQ4, which contains 6 transmembrane domains and a long cytoplasmic C-terminal tail, plays a crucial role in K+ recycling in the inner ear. Although KCNQ4 binds to various interactors, specific binding sites of the interactors remain elusive, and the biological significance of these interactions remains unknown. Therefore, this study aimed to discover a novel interactor of KCNQ4 and delineate its functional role in KCNQ4 regulation. We discovered a novel interactor of KCNQ4, huntingtin-associated protein 1 (HAP1), in addition to calmodulin, which interacts with the C-terminus of KCNQ4 using a yeast 2-hybrid assay. This interaction requires the B-segment of KCNQ4 as demonstrated by protein domain analysis. A thorough investigation of the biochemical and physiological consequences of this association revealed that HAP1 overexpression reduced surface expression and attenuated the potassium current mediated by KCNQ4. This suggests that HAP1 acts as a negative regulator of KCNQ4, potentially through the disruption of normal endocytic trafficking. These findings enhance the understanding of KCNQ4 regulation at the molecular level and highlight the potential of the HAP1-KCNQ4 axis as a target for interventions aimed at maintaining channel surface stability.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"49 3","pages":"Article 100322"},"PeriodicalIF":6.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Tankyrase-1-mediated PARsylation directs TFEB partner switching to regulate selective Wnt target gene expression tankyase -1介导的PARsylation指导TFEB伴侣转换以调节选择性Wnt靶基因的表达。

IF 6.5 3区生物学

Molecules and Cells Pub Date : 2026-03-01 Epub Date: 2026-01-08 DOI: 10.1016/j.mocell.2026.100313

Gahyeon Song , Chanhyeok Park , Eek-hoon Jho

{"title":"Tankyrase-1-mediated PARsylation directs TFEB partner switching to regulate selective Wnt target gene expression","authors":"Gahyeon Song , Chanhyeok Park , Eek-hoon Jho","doi":"10.1016/j.mocell.2026.100313","DOIUrl":"10.1016/j.mocell.2026.100313","url":null,"abstract":"<div><div>Wnt/β-catenin signaling coordinates developmental and oncogenic programs by modulating transcriptional networks. In addition to β-catenin, we previously identified transcription factor EB (TFEB)—a master regulator of lysosomal biogenesis and autophagy—as a Wnt-inducible co-regulator for a subset of Wnt target genes. However, the molecular mechanism underlying this selective transcriptional engagement remained unknown. Here, we show that Wnt3a stimulation promotes TFEB’s interaction with TCF-1/LEF-1 without altering lysosomal or autophagy-related gene regulation. This Wnt-specific association requires TFEB’s basic helix-loop-helix and leucine zipper domains and coincides with a marked reduction in TFEB-TFEB interaction. Mechanistically, Wnt activation triggers Tankyrase-1-mediated PARsylation of TFEB at K237 and K274 within the basic helix-loop-helix domain, switching its binding preference from homodimers to TCF-1/LEF-1 complexes. PARsylation-deficient TFEB mutants fail to associate with TCF-1/LEF-1 and cannot induce Wnt-TFEB target gene expression. These findings uncover a PARsylation-dependent partner-switching mechanism that reprograms TFEB’s transcriptional output under Wnt signaling.</div></div>","PeriodicalId":18795,"journal":{"name":"Molecules and Cells","volume":"49 3","pages":"Article 100313"},"PeriodicalIF":6.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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