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Annual review of biochemistry最新文献

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Extracellular Vesicles and Cellular Homeostasis.
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-03-18 DOI: 10.1146/annurev-biochem-100924-012717
Jordan Matthew Ngo, Justin Krish Williams, Congyan Zhang, Amr Hosny Saleh, Xiao-Man Liu, Liang Ma, Randy Schekman
{"title":"Extracellular Vesicles and Cellular Homeostasis.","authors":"Jordan Matthew Ngo, Justin Krish Williams, Congyan Zhang, Amr Hosny Saleh, Xiao-Man Liu, Liang Ma, Randy Schekman","doi":"10.1146/annurev-biochem-100924-012717","DOIUrl":"https://doi.org/10.1146/annurev-biochem-100924-012717","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are secreted, membrane-enclosed particles that have been proposed to play a broad role in intercellular communication. Most often, EVs, by analogy to enveloped viruses, are suggested to fuse to or within a target cell to deliver a soluble signaling molecule into the cytoplasm. However, significant evidence supports an alternative model in which EVs are secreted to promote homeostasis. In this model, EVs are loaded with unwanted or toxic cargo, secreted upon cellular or organismal stress, and degraded by other cells. Here, we present evidence supporting this homeostatic EV model and discuss the general inefficiency of EV cargo delivery. While the homeostatic and viral delivery models for EV function are not mutually exclusive, we propose that much of the evidence presented is hard to reconcile with a broad role for EVs in cargo transfer as a means to promote intercellular communication.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655887","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
Emerging Approaches for Studying Lipid Dynamics, Metabolism, and Interactions in Cells.
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-03-18 DOI: 10.1146/annurev-biochem-083024-110827
Lin Luan, Nathan P Frederick, Jeremy M Baskin
{"title":"Emerging Approaches for Studying Lipid Dynamics, Metabolism, and Interactions in Cells.","authors":"Lin Luan, Nathan P Frederick, Jeremy M Baskin","doi":"10.1146/annurev-biochem-083024-110827","DOIUrl":"https://doi.org/10.1146/annurev-biochem-083024-110827","url":null,"abstract":"<p><p>Lipids are a major class of biological molecules, the primary components of cellular membranes, and critical signaling molecules that regulate cell biology and physiology. Due to their dynamic behavior within membranes, rapid transport between organelles, and complex and often redundant metabolic pathways, lipids have traditionally been considered among the most challenging biological molecules to study. In recent years, a plethora of tools bridging the chemistry-biology interface has emerged for studying different aspects of lipid biology. Here, we provide an overview of these approaches. We discuss methods for lipid detection, including genetically encoded biosensors, synthetic lipid analogs, and metabolic labeling probes. For targeted manipulation of lipids, we describe pharmacological agents and controllable enzymes, termed membrane editors, that harness optogenetics and chemogenetics. To conclude, we survey techniques for elucidating lipid-protein interactions, including photoaffinity labeling and proximity labeling. Collectively, these strategies are revealing new insights into the regulation, dynamics, and functions of lipids in cell biology.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655884","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
Topoisomerase Regulation of Cancer Gene Expression.
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-03-18 DOI: 10.1146/annurev-biochem-091724-010717
Laura Baranello, Fedor Kouzine, David Levens
{"title":"Topoisomerase Regulation of Cancer Gene Expression.","authors":"Laura Baranello, Fedor Kouzine, David Levens","doi":"10.1146/annurev-biochem-091724-010717","DOIUrl":"https://doi.org/10.1146/annurev-biochem-091724-010717","url":null,"abstract":"<p><p>Under hyperproliferative conditions, escalation of genomic activity provokes high levels of DNA mechanical stress. Cancer cells cope with this stress through topoisomerase activity. Topoisomerases support genome-wide programs, including those driven by oncogenes and tumor suppressors, by adjusting the supercoiling and by interacting with the regulatory complexes involved in transcription, replication, and chromatin transactions. Topoisomerases also manage DNA conformational alterations that control gene activity. However, when the topological stress from oncogene-driven processes exceeds topoisomerase capacity, aberrant structures associated with DNA damage arise. These abnormalities include R-loop formation during transcription and replication. Excessive supercoiling also creates transcription-replication conflicts triggering DNA damage. Topoisomerase catalytic failure elicits topological dysregulation and DNA damage. This damage contributes further to tumorigenesis and tumor progression. The roles of topoisomerases in various genetic processes have been widely described, but the cancer-specific functions of topoisomerases are incompletely understood. Here, we summarize the crucial roles played by topoisomerases in cancer.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655566","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
Electron Transport Across Bacterial Cell Envelopes.
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-03-17 DOI: 10.1146/annurev-biochem-052621-092202
Joshua A J Burton, Marcus J Edwards, David J Richardson, Thomas A Clarke
{"title":"Electron Transport Across Bacterial Cell Envelopes.","authors":"Joshua A J Burton, Marcus J Edwards, David J Richardson, Thomas A Clarke","doi":"10.1146/annurev-biochem-052621-092202","DOIUrl":"https://doi.org/10.1146/annurev-biochem-052621-092202","url":null,"abstract":"<p><p>Extracellular electron transfer is an ancient and ubiquitous process that is used by a range of microorganisms to exchange electrons between the cell and environment. These electron transfer reactions can impact the solubility and speciation of redox-active molecules in the environment, such as metal oxides, while allowing bacteria to survive in areas of limited nutrient availability. Controlled transfer of electrons across the cell envelope requires assembly of electron transport chains that must pass through the outer membrane of Gram-negative bacteria or the S-layer of Gram-positive bacteria, but the mechanisms used by bacteria are still far from understood. Here, we review the literature surrounding characterized extracellular electron transfer pathways and use protein modeling tools to investigate novel electron transfer proteins and protein complexes. While these protein models are hypothetical, they provide new insight into features that may explain how extracellular electron transfer complexes interact with a range of different environmental substrates.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647213","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
Moonlighting Enzymes at the Interface Between Metabolism and Epigenetics.
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-03-17 DOI: 10.1146/annurev-biochem-030122-044718
Jan A van der Knaap, C Peter Verrijzer
{"title":"Moonlighting Enzymes at the Interface Between Metabolism and Epigenetics.","authors":"Jan A van der Knaap, C Peter Verrijzer","doi":"10.1146/annurev-biochem-030122-044718","DOIUrl":"https://doi.org/10.1146/annurev-biochem-030122-044718","url":null,"abstract":"<p><p>Metabolism and gene regulation are vital processes that need to be tightly coordinated to maintain homeostasis or to enable growth and development. Recent research has begun to reveal the surprisingly interlaced relationship between metabolism and gene expression control. Because key metabolites are cofactors or cosubstrates of chromatin-modifying enzymes, changes in their concentrations can modulate chromatin states and gene expression. Additionally, an increasing number of key metabolic enzymes are found to directly regulate chromatin and transcription in response to changes in metabolic state. These include enzymes that fuel chromatin-associated metabolism and moonlighting enzymes that function as transcription factors, independent of their enzymatic activity. Conversely, accumulating evidence suggests that chromatin itself serves key metabolic functions, independent of transcriptional regulation. Here, we discuss the bidirectional interface between metabolism and chromatin and its corruption in cancer cells.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647217","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
Lipid Dynamics at Membrane Contact Sites.
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2025-03-11 DOI: 10.1146/annurev-biochem-083024-122821
Karin M Reinisch, Pietro De Camilli, Thomas J Melia
{"title":"Lipid Dynamics at Membrane Contact Sites.","authors":"Karin M Reinisch, Pietro De Camilli, Thomas J Melia","doi":"10.1146/annurev-biochem-083024-122821","DOIUrl":"https://doi.org/10.1146/annurev-biochem-083024-122821","url":null,"abstract":"<p><p>In eukaryotes, lipid building blocks for cellular membranes are made largely in the endoplasmic reticulum and then redistributed to other organelles. Lipids are transported between organelles by vesicular trafficking or else by proteins located primarily at sites where different organelles are closely apposed. Here we discuss transport at organelle contact sites mediated by shuttle-like proteins that carry single lipids between membranes to fine-tune their composition and by the more recently discovered bridge-like proteins that tether two organelles and provide a path for bulk lipid movement. Protein-mediated lipid transport is assisted by integral membrane proteins that have roles in (<i>a</i>) lowering the energy barrier for lipid transfer between the membrane and the lipid transfer protein, a key parameter determining the transfer rate, and (<i>b</i>) scrambling lipids to counteract the bilayer asymmetry that would result from such transfer. Advances in this field are shedding new light on a variety of physiological mechanisms.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603653","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 Lipid-Raft Theory of Alzheimer's Disease. 阿尔茨海默病的脂质筏理论
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-10-30 DOI: 10.1146/annurev-biochem-052024-115455
Ari Rappoport
{"title":"A Lipid-Raft Theory of Alzheimer's Disease.","authors":"Ari Rappoport","doi":"10.1146/annurev-biochem-052024-115455","DOIUrl":"https://doi.org/10.1146/annurev-biochem-052024-115455","url":null,"abstract":"<p><p>I present a theory of Alzheimer's disease (AD) that explains its symptoms, pathology, and risk factors. To do this, I introduce a new theory of brain plasticity that elucidates the physiological roles of AD-related agents. New events generate synaptic and branching candidates competing for long-term enhancement. Competition resolution crucially depends on the formation of membrane lipid rafts, which requires astrocyte-produced cholesterol. Sporadic AD is caused by impaired formation of plasma-membrane lipid rafts, preventing the conversion of short- to long-term memory and yielding excessive tau phosphorylation, intracellular cholesterol accumulation, synaptic dysfunction, and neurodegeneration. Amyloid β (Aβ) production is promoted by cholesterol during the switch to competition resolution, and cholesterol accumulation stimulates chronic Aβ production, secretion, and aggregation. The theory addresses all of the major established facts known about the disease and is supported by strong evidence.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":""},"PeriodicalIF":12.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543236","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
Inositol Pyrophosphates as Versatile Metabolic Messengers. 作为多功能代谢信使的肌醇焦磷酸盐
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-08-01 DOI: 10.1146/annurev-biochem-030222-121901
Latika Nagpal, Sining He, Feng Rao, Solomon H Snyder
{"title":"Inositol Pyrophosphates as Versatile Metabolic Messengers.","authors":"Latika Nagpal, Sining He, Feng Rao, Solomon H Snyder","doi":"10.1146/annurev-biochem-030222-121901","DOIUrl":"https://doi.org/10.1146/annurev-biochem-030222-121901","url":null,"abstract":"<p><p>Discovered in 1993, inositol pyrophosphates are evolutionarily conserved signaling metabolites whose versatile modes of action are being increasingly appreciated. These include their emerging roles as energy regulators, phosphodonors, steric/allosteric regulators, and G protein-coupled receptor messengers. Through studying enzymes that metabolize inositol pyrophosphates, progress has also been made in elucidating the various cellular and physiological functions of these pyrophosphate-containing, energetic molecules. The two main forms of inositol pyrophosphates, 5-IP<sub>7</sub> and IP<sub>8</sub>, synthesized respectively by inositol-hexakisphosphate kinases (IP6Ks) and diphosphoinositol pentakisphosphate kinases (PPIP5Ks), regulate phosphate homeostasis, ATP synthesis, and several other metabolic processes ranging from insulin secretion to cellular energy utilization. Here, we review the current understanding of the catalytic and regulatory mechanisms of IP6Ks and PPIP5Ks, as well as their counteracting phosphatases. We also highlight the genetic and cellular evidence implicating inositol pyrophosphates as essential mediators of mammalian metabolic homeostasis.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":"93 1","pages":"317-338"},"PeriodicalIF":12.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878241","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 Nicotinic Acetylcholine Receptor and Its Pentameric Homologs: Toward an Allosteric Mechanism of Signal Transduction at the Atomic Level. 烟碱乙酰胆碱受体及其五聚体同源物：在原子水平上实现信号转导的异构机制。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-08-01 Epub Date: 2024-07-02 DOI: 10.1146/annurev-biochem-030122-033116
Marco Cecchini, Pierre-Jean Corringer, Jean-Pierre Changeux
{"title":"The Nicotinic Acetylcholine Receptor and Its Pentameric Homologs: Toward an Allosteric Mechanism of Signal Transduction at the Atomic Level.","authors":"Marco Cecchini, Pierre-Jean Corringer, Jean-Pierre Changeux","doi":"10.1146/annurev-biochem-030122-033116","DOIUrl":"10.1146/annurev-biochem-030122-033116","url":null,"abstract":"<p><p>The nicotinic acetylcholine receptor has served, since its biochemical identification in the 1970s, as a model of an allosteric ligand-gated ion channel mediating signal transition at the synapse. In recent years, the application of X-ray crystallography and high-resolution cryo-electron microscopy, together with molecular dynamic simulations of nicotinic receptors and homologs, have opened a new era in the understanding of channel gating by the neurotransmitter. They reveal, at atomic resolution, the diversity and flexibility of the multiple ligand-binding sites, including recently discovered allosteric modulatory sites distinct from the neurotransmitter orthosteric site, and the conformational dynamics of the activation process as a molecular switch linking these multiple sites. The model emerging from these studies paves the way for a new pharmacology based, first, upon the occurrence of an original mode of indirect allosteric modulation, distinct from a steric competition for a single and rigid binding site, and second, the design of drugs that specifically interact with privileged conformations of the receptor such as agonists, antagonists, and desensitizers. Research on nicotinic receptors is still at the forefront of understanding the mode of action of drugs on the nervous system.</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"339-366"},"PeriodicalIF":12.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721266","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
Signaling from RAS to RAF: The Molecules and Their Mechanisms. 从 RAS 到 RAF 的信号传递：分子及其机制。
IF 12.1 1区 生物学
Annual review of biochemistry Pub Date : 2024-08-01 Epub Date: 2024-07-02 DOI: 10.1146/annurev-biochem-052521-040754
Hyesung Jeon, Emre Tkacik, Michael J Eck
{"title":"Signaling from RAS to RAF: The Molecules and Their Mechanisms.","authors":"Hyesung Jeon, Emre Tkacik, Michael J Eck","doi":"10.1146/annurev-biochem-052521-040754","DOIUrl":"10.1146/annurev-biochem-052521-040754","url":null,"abstract":"<p><p>RAF family protein kinases are a key node in the RAS/RAF/MAP kinase pathway, the signaling cascade that controls cellular proliferation, differentiation, and survival in response to engagement of growth factor receptors on the cell surface. Over the past few years, structural and biochemical studies have provided new understanding of RAF autoregulation, RAF activation by RAS and the SHOC2 phosphatase complex, and RAF engagement with HSP90-CDC37 chaperone complexes. These studies have important implications for pharmacologic targeting of the pathway. They reveal RAF in distinct regulatory states and show that the functional RAF switch is an integrated complex of RAF with its substrate (MEK) and a 14-3-3 dimer. Here we review these advances, placing them in the context of decades of investigation of RAF regulation. We explore the insights they provide into aberrant activation of the pathway in cancer and RASopathies (developmental syndromes caused by germline mutations in components of the pathway).</p>","PeriodicalId":7980,"journal":{"name":"Annual review of biochemistry","volume":" ","pages":"289-316"},"PeriodicalIF":12.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139691045","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
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