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Regulation of and challenges in targeting NAD+ metabolism 针对 NAD+ 代谢的调节和挑战。
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-07-18 DOI: 10.1038/s41580-024-00752-w
Marie E. Migaud, Mathias Ziegler, Joseph A. Baur
{"title":"Regulation of and challenges in targeting NAD+ metabolism","authors":"Marie E. Migaud, Mathias Ziegler, Joseph A. Baur","doi":"10.1038/s41580-024-00752-w","DOIUrl":"10.1038/s41580-024-00752-w","url":null,"abstract":"Nicotinamide adenine dinucleotide, in its oxidized (NAD+) and reduced (NADH) forms, is a reduction–oxidation (redox) co-factor and substrate for signalling enzymes that have essential roles in metabolism. The recognition that NAD+ levels fall in response to stress and can be readily replenished through supplementation has fostered great interest in the potential benefits of increasing or restoring NAD+ levels in humans to prevent or delay diseases and degenerative processes. However, much about the biology of NAD+ and related molecules remains poorly understood. In this Review, we discuss the current knowledge of NAD+ metabolism, including limitations of, assumptions about and unappreciated factors that might influence the success or contribute to risks of NAD+ supplementation. We highlight several ongoing controversies in the field, and discuss the role of the microbiome in modulating the availability of NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), the presence of multiple cellular compartments that have distinct pools of NAD+ and NADH, and non-canonical NAD+ and NADH degradation pathways. We conclude that a substantial investment in understanding the fundamental biology of NAD+, its detection and its metabolites in specific cells and cellular compartments is needed to support current translational efforts to safely boost NAD+ levels in humans. Nicotinamide adenine dinucleotide (NAD+) has essential roles in metabolism and can be readily supplemented, potentially to benefit human health. This Review discusses recent insights into the roles of the microbiome and cellular compartments in regulating NAD+ metabolism, and the promise and pitfalls of NAD+ supplementation.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 10","pages":"822-840"},"PeriodicalIF":81.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723970","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
Cellular and pathological functions of tau tau 的细胞和病理功能
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-07-16 DOI: 10.1038/s41580-024-00753-9
Celeste Parra Bravo, Sarah A. Naguib, Li Gan
{"title":"Cellular and pathological functions of tau","authors":"Celeste Parra Bravo, Sarah A. Naguib, Li Gan","doi":"10.1038/s41580-024-00753-9","DOIUrl":"10.1038/s41580-024-00753-9","url":null,"abstract":"Tau protein is involved in various cellular processes, including having a canonical role in binding and stabilization of microtubules in neurons. Tauopathies are neurodegenerative diseases marked by the abnormal accumulation of tau protein aggregates in neurons, as seen, for example, in conditions such as frontotemporal dementia and Alzheimer disease. Mutations in tau coding regions or that disrupt tau mRNA splicing, tau post-translational modifications and cellular stress factors (such as oxidative stress and inflammation) increase the tendency of tau to aggregate and interfere with its clearance. Pathological tau is strongly implicated in the progression of neurodegenerative diseases, and the propagation of tau aggregates is associated with disease severity. Recent technological advancements, including cryo-electron microscopy and disease models derived from human induced pluripotent stem cells, have increased our understanding of tau-related pathology in neurodegenerative conditions. Substantial progress has been made in deciphering tau aggregate structures and the molecular mechanisms that underlie protein aggregation and toxicity. In this Review, we discuss recent insights into the diverse cellular functions of tau and the pathology of tau inclusions and explore the potential for therapeutic interventions. Tau is a microtubule-binding protein that is expressed primarily in neurons. The abnormal accumulation of tau aggregates in neurons is associated with neurodegenerative diseases, known as tauopathies, such as Alzheimer disease and frontotemporal dementia. This Review discusses recent insights into the diverse cellular functions of tau, the pathology of tau aggregates and the potential for therapeutic interventions.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 11","pages":"845-864"},"PeriodicalIF":81.3,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625090","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
The discovery of cyclin-dependent kinases 依赖细胞周期蛋白的激酶的发现
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-07-15 DOI: 10.1038/s41580-024-00765-5
Paul Nurse
{"title":"The discovery of cyclin-dependent kinases","authors":"Paul Nurse","doi":"10.1038/s41580-024-00765-5","DOIUrl":"10.1038/s41580-024-00765-5","url":null,"abstract":"Paul Nurse discusses how a 1971 paper by Culotti and Hartwell inspired him to investigate the cell cycle in fission yeast, and how these genetics studies led to the discovery of cyclin-dependent kinases.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 10","pages":"763-763"},"PeriodicalIF":81.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141618206","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
Virus–host warfare by PROTACs PROTAC 的病毒-宿主战争
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-07-09 DOI: 10.1038/s41580-024-00761-9
Kylie J. Walters
{"title":"Virus–host warfare by PROTACs","authors":"Kylie J. Walters","doi":"10.1038/s41580-024-00761-9","DOIUrl":"10.1038/s41580-024-00761-9","url":null,"abstract":"The studies that paved the way for the development of PROTACs (proteolysis-targeting chimeras) as therapeutic strategies, and the HPV vaccine.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 9","pages":"675-675"},"PeriodicalIF":81.3,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561352","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
Long-lived proteomes in healthy ovaries 健康卵巢中的长寿命蛋白质组
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-07-05 DOI: 10.1038/s41580-024-00764-6
Eytan Zlotorynski
{"title":"Long-lived proteomes in healthy ovaries","authors":"Eytan Zlotorynski","doi":"10.1038/s41580-024-00764-6","DOIUrl":"10.1038/s41580-024-00764-6","url":null,"abstract":"Many proteins in the mouse ovary are extremely stable; they enhance proteostasis and limit protein aggregation, thereby supporting the maintenance of the long-lived oocytes.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 8","pages":"596-596"},"PeriodicalIF":81.3,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538245","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
Heterochromatin as a balancing act between transcription and gene silencing 异染色质是转录和基因沉默之间的平衡。
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-07-03 DOI: 10.1038/s41580-024-00762-8
Sigurd Braun
{"title":"Heterochromatin as a balancing act between transcription and gene silencing","authors":"Sigurd Braun","doi":"10.1038/s41580-024-00762-8","DOIUrl":"10.1038/s41580-024-00762-8","url":null,"abstract":"An elegant study revealed the distinct roles of different H3K9 methylation states in heterochromatin formation and function.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 9","pages":"676-676"},"PeriodicalIF":81.3,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498535","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
Resolution in super-resolution microscopy — definition, trade-offs and perspectives 超分辨率显微镜的分辨率--定义、权衡与展望。
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1038/s41580-024-00755-7
Kirti Prakash, David Baddeley, Christian Eggeling, Reto Fiolka, Rainer Heintzmann, Suliana Manley, Aleksandra Radenovic, Carlas Smith, Hari Shroff, Lothar Schermelleh
{"title":"Resolution in super-resolution microscopy — definition, trade-offs and perspectives","authors":"Kirti Prakash, David Baddeley, Christian Eggeling, Reto Fiolka, Rainer Heintzmann, Suliana Manley, Aleksandra Radenovic, Carlas Smith, Hari Shroff, Lothar Schermelleh","doi":"10.1038/s41580-024-00755-7","DOIUrl":"10.1038/s41580-024-00755-7","url":null,"abstract":"Super-resolution microscopy (SRM) is gaining popularity in biosciences; however, claims about optical resolution are contested and often misleading. In this Viewpoint, experts share their views on resolution and common trade-offs, such as labelling and post-processing, aiming to clarify them for biologists and facilitate deeper understanding and best use of SRM. In this Viewpoint, experts discuss resolution and common trade-offs in super-resolution microscopy, aiming to improve how biologists use the technology.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 9","pages":"677-682"},"PeriodicalIF":81.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477009","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
Pitfalls in lipid mass spectrometry of mammalian samples — a brief guide for biologists 哺乳动物样本脂质质谱分析中的误区--生物学家简明指南。
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1038/s41580-024-00758-4
Tore Skotland, Kim Ekroos, Jeffrey McDonald, Robert Ahrends, Gerhard Liebisch, Kirsten Sandvig
{"title":"Pitfalls in lipid mass spectrometry of mammalian samples — a brief guide for biologists","authors":"Tore Skotland, Kim Ekroos, Jeffrey McDonald, Robert Ahrends, Gerhard Liebisch, Kirsten Sandvig","doi":"10.1038/s41580-024-00758-4","DOIUrl":"10.1038/s41580-024-00758-4","url":null,"abstract":"This Comment discusses erroneous reporting of mass spectrometry analyses of lipids in mammalian samples, and provides recommendations for how to avoid it. Publications that report mass spectrometry analyses of lipids often include lipid species that probably do not exist in the samples. Here we provide recommendations for scientists on submitting lipid data, and for reviewers, editors and readers on evaluating these data, to reduce the reporting of erroneous lipid species.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 10","pages":"759-760"},"PeriodicalIF":81.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477007","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
Polarized endoplasmic reticulum–plasma membrane contacts in cell migration 细胞迁移中的极化内质网-质膜接触。
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-07-01 DOI: 10.1038/s41580-024-00759-3
Lisa Heinke
{"title":"Polarized endoplasmic reticulum–plasma membrane contacts in cell migration","authors":"Lisa Heinke","doi":"10.1038/s41580-024-00759-3","DOIUrl":"10.1038/s41580-024-00759-3","url":null,"abstract":"In a recent study, Bong et al. identify a polarized distribution of contact sites between the endoplasmic reticulum and plasma membrane in migrating cells, whereby higher density of contacts in the back of the cells prevents the formation of additional migration fronts.","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 8","pages":"595-595"},"PeriodicalIF":81.3,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477008","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
Author Correction: Mechanisms controlling cellular and systemic iron homeostasis 作者更正：控制细胞和全身铁平衡的机制。
IF 81.3 1区 生物学
Nature Reviews Molecular Cell Biology Pub Date : 2024-06-26 DOI: 10.1038/s41580-024-00760-w
Bruno Galy, Marcus Conrad, Martina Muckenthaler
{"title":"Author Correction: Mechanisms controlling cellular and systemic iron homeostasis","authors":"Bruno Galy, Marcus Conrad, Martina Muckenthaler","doi":"10.1038/s41580-024-00760-w","DOIUrl":"10.1038/s41580-024-00760-w","url":null,"abstract":"","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"25 8","pages":"671-671"},"PeriodicalIF":81.3,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41580-024-00760-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141458257","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
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