Pub Date : 2023-01-01DOI: 10.1152/physrev.00051.2021
Ronald J A Wanders, Myriam Baes, Daniela Ribeiro, Sacha Ferdinandusse, Hans R Waterham
Peroxisomes are subcellular organelles that play a central role in human physiology by catalyzing a range of unique metabolic functions. The importance of peroxisomes for human health is exemplified by the existence of a group of usually severe diseases caused by an impairment in one or more peroxisomal functions. Among others these include the Zellweger spectrum disorders, X-linked adrenoleukodystrophy, and Refsum disease. To fulfill their role in metabolism, peroxisomes require continued interaction with other subcellular organelles including lipid droplets, lysosomes, the endoplasmic reticulum, and mitochondria. In recent years it has become clear that the metabolic alliance between peroxisomes and other organelles requires the active participation of tethering proteins to bring the organelles physically closer together, thereby achieving efficient transfer of metabolites. This review intends to describe the current state of knowledge about the metabolic role of peroxisomes in humans, with particular emphasis on the metabolic partnership between peroxisomes and other organelles and the consequences of genetic defects in these processes. We also describe the biogenesis of peroxisomes and the consequences of the multiple genetic defects therein. In addition, we discuss the functional role of peroxisomes in different organs and tissues and include relevant information derived from model systems, notably peroxisomal mouse models. Finally, we pay particular attention to a hitherto underrated role of peroxisomes in viral infections.
{"title":"The physiological functions of human peroxisomes.","authors":"Ronald J A Wanders, Myriam Baes, Daniela Ribeiro, Sacha Ferdinandusse, Hans R Waterham","doi":"10.1152/physrev.00051.2021","DOIUrl":"https://doi.org/10.1152/physrev.00051.2021","url":null,"abstract":"<p><p>Peroxisomes are subcellular organelles that play a central role in human physiology by catalyzing a range of unique metabolic functions. The importance of peroxisomes for human health is exemplified by the existence of a group of usually severe diseases caused by an impairment in one or more peroxisomal functions. Among others these include the Zellweger spectrum disorders, X-linked adrenoleukodystrophy, and Refsum disease. To fulfill their role in metabolism, peroxisomes require continued interaction with other subcellular organelles including lipid droplets, lysosomes, the endoplasmic reticulum, and mitochondria. In recent years it has become clear that the metabolic alliance between peroxisomes and other organelles requires the active participation of tethering proteins to bring the organelles physically closer together, thereby achieving efficient transfer of metabolites. This review intends to describe the current state of knowledge about the metabolic role of peroxisomes in humans, with particular emphasis on the metabolic partnership between peroxisomes and other organelles and the consequences of genetic defects in these processes. We also describe the biogenesis of peroxisomes and the consequences of the multiple genetic defects therein. In addition, we discuss the functional role of peroxisomes in different organs and tissues and include relevant information derived from model systems, notably peroxisomal mouse models. Finally, we pay particular attention to a hitherto underrated role of peroxisomes in viral infections.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":null,"pages":null},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10400622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2022-09-01DOI: 10.1152/physrev.00028.2022
John P A Ioannidis
{"title":"Systematic reviews for basic scientists: a different beast.","authors":"John P A Ioannidis","doi":"10.1152/physrev.00028.2022","DOIUrl":"https://doi.org/10.1152/physrev.00028.2022","url":null,"abstract":"","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":null,"pages":null},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40337904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neutrophil extracellular trap (NET) formation, first described in 2004 as a previously unknown strategy of neutrophils to fight microbes, has attracted an increasing interest in the research community. NETs are formed when neutrophils externalize their decondensed chromatin together with content from their azurophilic granules. In addition to their role in defense against microbes, NETs have been implicated as mediators of pathology in sterile inflammation, such as cancer and autoimmunity, and their potential as therapeutic targets is actively explored. However, targeting of NETs is challenging since the beneficial effects of their removal need to be balanced against the potential harmful loss of their function in microbial defense. Moreover, depending on the stimuli or species, NETs can be formed via distinct mechanisms and are not always made up of the same components, making direct comparisons between various studies challenging. This review focuses on the role of NETs in cancer-associated pathology, such as thrombosis, organ dysfunction, and metastasis. Different strategies to target NETs, by either preventing their formation or degrading existing ones, are also discussed.
{"title":"Neutrophil extracellular traps in the pathology of cancer and other inflammatory diseases.","authors":"Melanie Herre, Jessica Cedervall, Nigel Mackman, Anna-Karin Olsson","doi":"10.1152/physrev.00062.2021","DOIUrl":"10.1152/physrev.00062.2021","url":null,"abstract":"<p><p>Neutrophil extracellular trap (NET) formation, first described in 2004 as a previously unknown strategy of neutrophils to fight microbes, has attracted an increasing interest in the research community. NETs are formed when neutrophils externalize their decondensed chromatin together with content from their azurophilic granules. In addition to their role in defense against microbes, NETs have been implicated as mediators of pathology in sterile inflammation, such as cancer and autoimmunity, and their potential as therapeutic targets is actively explored. However, targeting of NETs is challenging since the beneficial effects of their removal need to be balanced against the potential harmful loss of their function in microbial defense. Moreover, depending on the stimuli or species, NETs can be formed via distinct mechanisms and are not always made up of the same components, making direct comparisons between various studies challenging. This review focuses on the role of NETs in cancer-associated pathology, such as thrombosis, organ dysfunction, and metastasis. Different strategies to target NETs, by either preventing their formation or degrading existing ones, are also discussed.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":null,"pages":null},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40698536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2022-08-11DOI: 10.1152/physrev.00052.2021
Natalie R Harris, László Bálint, Danielle M Dy, Natalie R Nielsen, Hernán G Méndez, Amir Aghajanian, Kathleen M Caron
The heart is imbued with a vast lymphatic network that is responsible for fluid homeostasis and immune cell trafficking. Disturbances in the forces that regulate microvascular fluid movement can result in myocardial edema, which has profibrotic and proinflammatory consequences and contributes to cardiovascular dysfunction. This review explores the complex relationship between cardiac lymphatics, myocardial edema, and cardiac disease. It covers the revised paradigm of microvascular forces and fluid movement around the capillary as well as the arsenal of preclinical tools and animal models used to model myocardial edema and cardiac disease. Clinical studies of myocardial edema and their prognostic significance are examined in parallel to the recent elegant animal studies discerning the pathophysiological role and therapeutic potential of cardiac lymphatics in different cardiovascular disease models. This review highlights the outstanding questions of interest to both basic scientists and clinicians regarding the roles of cardiac lymphatics in health and disease.
{"title":"The ebb and flow of cardiac lymphatics: a tidal wave of new discoveries.","authors":"Natalie R Harris, László Bálint, Danielle M Dy, Natalie R Nielsen, Hernán G Méndez, Amir Aghajanian, Kathleen M Caron","doi":"10.1152/physrev.00052.2021","DOIUrl":"10.1152/physrev.00052.2021","url":null,"abstract":"<p><p>The heart is imbued with a vast lymphatic network that is responsible for fluid homeostasis and immune cell trafficking. Disturbances in the forces that regulate microvascular fluid movement can result in myocardial edema, which has profibrotic and proinflammatory consequences and contributes to cardiovascular dysfunction. This review explores the complex relationship between cardiac lymphatics, myocardial edema, and cardiac disease. It covers the revised paradigm of microvascular forces and fluid movement around the capillary as well as the arsenal of preclinical tools and animal models used to model myocardial edema and cardiac disease. Clinical studies of myocardial edema and their prognostic significance are examined in parallel to the recent elegant animal studies discerning the pathophysiological role and therapeutic potential of cardiac lymphatics in different cardiovascular disease models. This review highlights the outstanding questions of interest to both basic scientists and clinicians regarding the roles of cardiac lymphatics in health and disease.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":null,"pages":null},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40619045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of disorders characterized by early-onset, often severe epileptic seizures and EEG abnormalities on a background of developmental impairment that tends to worsen as a consequence of epilepsy. DEEs may result from both nongenetic and genetic etiologies. Genetic DEEs have been associated with mutations in many genes involved in different functions including cell migration, proliferation, and organization, neuronal excitability, and synapse transmission and plasticity. Functional studies performed in different animal models and clinical trials on patients have contributed to elucidate pathophysiological mechanisms underlying many DEEs and have explored the efficacy of different treatments. Here, we provide an extensive review of the phenotypic spectrum included in the DEEs and of the genetic determinants and pathophysiological mechanisms underlying these conditions. We also provide a brief overview of the most effective treatment now available and of the emerging therapeutic approaches.
发育性和癫痫性脑病(DEEs)是一组异质性疾病,其特征是在发育障碍的背景下,出现早发、通常严重的癫痫发作和脑电图异常,而发育障碍往往会因癫痫而恶化。DEE 既可能是非遗传性的,也可能是遗传性的。遗传性 DEE 与许多涉及不同功能的基因突变有关,这些功能包括细胞迁移、增殖和组织、神经元兴奋性以及突触传递和可塑性。在不同动物模型中进行的功能研究和对患者进行的临床试验有助于阐明许多 DEEs 的病理生理机制,并探索不同治疗方法的疗效。在此,我们对 DEEs 的表型谱以及这些疾病的遗传决定因素和病理生理机制进行了广泛的综述。我们还简要介绍了目前最有效的治疗方法和新出现的治疗方法。
{"title":"Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum.","authors":"Renzo Guerrini, Valerio Conti, Massimo Mantegazza, Simona Balestrini, Aristea S Galanopoulou, Fabio Benfenati","doi":"10.1152/physrev.00063.2021","DOIUrl":"10.1152/physrev.00063.2021","url":null,"abstract":"<p><p>Developmental and epileptic encephalopathies (DEEs) are a heterogeneous group of disorders characterized by early-onset, often severe epileptic seizures and EEG abnormalities on a background of developmental impairment that tends to worsen as a consequence of epilepsy. DEEs may result from both nongenetic and genetic etiologies. Genetic DEEs have been associated with mutations in many genes involved in different functions including cell migration, proliferation, and organization, neuronal excitability, and synapse transmission and plasticity. Functional studies performed in different animal models and clinical trials on patients have contributed to elucidate pathophysiological mechanisms underlying many DEEs and have explored the efficacy of different treatments. Here, we provide an extensive review of the phenotypic spectrum included in the DEEs and of the genetic determinants and pathophysiological mechanisms underlying these conditions. We also provide a brief overview of the most effective treatment now available and of the emerging therapeutic approaches.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":null,"pages":null},"PeriodicalIF":29.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9296409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1152/physrev.00061.2021
Rosario B Jaime-Lara, Brianna E Brooks, Carlotta Vizioli, Mari Chiles, Nafisa Nawal, Rodrigo S E Ortiz-Figueroa, Alicia A Livinski, Khushbu Agarwal, Claudia Colina-Prisco, Natalia Iannarino, Aliya Hilmi, Hugo A Tejeda, Paule V Joseph
Taste and smell play a key role in our ability to perceive foods. Overconsumption of highly palatable energy-dense foods can lead to increased caloric intake and obesity. Thus there is growing interest in the study of the biological mediators of fat taste and associated olfaction as potential targets for pharmacologic and nutritional interventions in the context of obesity and health. The number of studies examining mechanisms underlying fat taste and smell has grown rapidly in the last 5 years. Therefore, the purpose of this systematic review is to summarize emerging evidence examining the biological mechanisms of fat taste and smell. A literature search was conducted of studies published in English between 2014 and 2021 in adult humans and animal models. Database searches were conducted using PubMed, EMBASE, Scopus, and Web of Science for key terms including fat/lipid, taste, and olfaction. Initially, 4,062 articles were identified through database searches, and a total of 84 relevant articles met inclusion and exclusion criteria and are included in this review. Existing literature suggests that there are several proteins integral to fat chemosensation, including cluster of differentiation 36 (CD36) and G protein-coupled receptor 120 (GPR120). This systematic review will discuss these proteins and the signal transduction pathways involved in fat detection. We also review neural circuits, key brain regions, ingestive cues, postingestive signals, and genetic polymorphism that play a role in fat perception and consumption. Finally, we discuss the role of fat taste and smell in the context of eating behavior and obesity.
味觉和嗅觉在我们感知食物的能力中起着关键作用。过度食用美味的高能量食物会导致热量摄入增加和肥胖。因此,人们对脂肪味觉和相关嗅觉的生物介质的研究越来越感兴趣,因为它们可以作为肥胖和健康背景下的药物和营养干预的潜在目标。在过去的5年里,研究脂肪味觉和嗅觉机制的研究数量迅速增长。因此,本系统综述的目的是总结研究脂肪味觉和嗅觉生物学机制的新证据。研究人员对2014年至2021年间发表的以成人和动物为模型的英文研究进行了文献检索。使用PubMed、EMBASE、Scopus和Web of Science进行数据库搜索,搜索关键术语包括脂肪/脂质、味道和嗅觉。最初,通过数据库检索确定了4,062篇文章,共有84篇相关文章符合纳入和排除标准,被纳入本综述。现有文献表明,脂肪化学感觉有几种不可或缺的蛋白质,包括分化簇36 (CD36)和G蛋白偶联受体120 (GPR120)。这篇系统的综述将讨论这些蛋白质和参与脂肪检测的信号转导途径。我们还回顾了在脂肪感知和消耗中发挥作用的神经回路、关键脑区、摄入线索、摄入后信号和基因多态性。最后,我们讨论了脂肪的味觉和嗅觉在饮食行为和肥胖的背景下的作用。
{"title":"A systematic review of the biological mediators of fat taste and smell.","authors":"Rosario B Jaime-Lara, Brianna E Brooks, Carlotta Vizioli, Mari Chiles, Nafisa Nawal, Rodrigo S E Ortiz-Figueroa, Alicia A Livinski, Khushbu Agarwal, Claudia Colina-Prisco, Natalia Iannarino, Aliya Hilmi, Hugo A Tejeda, Paule V Joseph","doi":"10.1152/physrev.00061.2021","DOIUrl":"https://doi.org/10.1152/physrev.00061.2021","url":null,"abstract":"<p><p>Taste and smell play a key role in our ability to perceive foods. Overconsumption of highly palatable energy-dense foods can lead to increased caloric intake and obesity. Thus there is growing interest in the study of the biological mediators of fat taste and associated olfaction as potential targets for pharmacologic and nutritional interventions in the context of obesity and health. The number of studies examining mechanisms underlying fat taste and smell has grown rapidly in the last 5 years. Therefore, the purpose of this systematic review is to summarize emerging evidence examining the biological mechanisms of fat taste and smell. A literature search was conducted of studies published in English between 2014 and 2021 in adult humans and animal models. Database searches were conducted using PubMed, EMBASE, Scopus, and Web of Science for key terms including fat/lipid, taste, and olfaction. Initially, 4,062 articles were identified through database searches, and a total of 84 relevant articles met inclusion and exclusion criteria and are included in this review. Existing literature suggests that there are several proteins integral to fat chemosensation, including cluster of differentiation 36 (CD36) and G protein-coupled receptor 120 (GPR120). This systematic review will discuss these proteins and the signal transduction pathways involved in fat detection. We also review neural circuits, key brain regions, ingestive cues, postingestive signals, and genetic polymorphism that play a role in fat perception and consumption. Finally, we discuss the role of fat taste and smell in the context of eating behavior and obesity.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":null,"pages":null},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9678415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10079977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2022-08-18DOI: 10.1152/physrev.00031.2021
Jorge Domínguez-Andrés, Jéssica Cristina Dos Santos, Siroon Bekkering, Willem J M Mulder, Jos W M van der Meer, Niels P Riksen, Leo A B Joosten, Mihai G Netea
The mechanisms underlying innate immune memory have been extensively explored in the last decades but are in fact largely unknown. Although the specificity of adaptive immune memory in vertebrates is ensured through the recombination of immunoglobulin family genes and clonal expansion, the basic mechanisms of innate immune cells' nonspecific increased responsiveness rely on epigenetic, transcriptional, and metabolic programs after transient stimulation. Changes in these programs result in enhanced responsiveness to secondary challenges with a wide variety of stimuli. This phenomenon is termed "trained immunity" or "innate immune memory." On one hand, trained immunity improves the response to infections and vaccination, facilitating stronger innate immune responses and enhanced protection against a variety of microbial stimuli. Conversely, trained immunity may contribute to the pathophysiology of cardiovascular, autoinflammatory, and neurodegenerative diseases. In this review, we gather the current body of knowledge in this field and summarize the foundations and mechanisms of trained immunity, the different cell types involved, its consequences for health and disease, and the potential of its modulation as a therapeutic tool.
{"title":"Trained immunity: adaptation within innate immune mechanisms.","authors":"Jorge Domínguez-Andrés, Jéssica Cristina Dos Santos, Siroon Bekkering, Willem J M Mulder, Jos W M van der Meer, Niels P Riksen, Leo A B Joosten, Mihai G Netea","doi":"10.1152/physrev.00031.2021","DOIUrl":"https://doi.org/10.1152/physrev.00031.2021","url":null,"abstract":"<p><p>The mechanisms underlying innate immune memory have been extensively explored in the last decades but are in fact largely unknown. Although the specificity of adaptive immune memory in vertebrates is ensured through the recombination of immunoglobulin family genes and clonal expansion, the basic mechanisms of innate immune cells' nonspecific increased responsiveness rely on epigenetic, transcriptional, and metabolic programs after transient stimulation. Changes in these programs result in enhanced responsiveness to secondary challenges with a wide variety of stimuli. This phenomenon is termed \"trained immunity\" or \"innate immune memory.\" On one hand, trained immunity improves the response to infections and vaccination, facilitating stronger innate immune responses and enhanced protection against a variety of microbial stimuli. Conversely, trained immunity may contribute to the pathophysiology of cardiovascular, autoinflammatory, and neurodegenerative diseases. In this review, we gather the current body of knowledge in this field and summarize the foundations and mechanisms of trained immunity, the different cell types involved, its consequences for health and disease, and the potential of its modulation as a therapeutic tool.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":null,"pages":null},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40424776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2022-08-18DOI: 10.1152/physrev.00009.2022
Spencer A Freeman, Sergio Grinstein, John Orlowski
The protonation state of soluble and membrane-associated macromolecules dictates their charge, conformation, and functional activity. In addition, protons (H+ or their equivalents) partake in numerous metabolic reactions and serve as a source of electrochemical energy to drive the transmembrane transport of both organic and inorganic substrates. Stringent regulation of the intracellular pH is therefore paramount to homeostasis. Although the regulation of the cytosolic pH has been studied extensively, our understanding of the determinants of the H+ concentration ([H+]) of intracellular organelles has developed more slowly, limited by their small size and inaccessibility. Recently, however, targeting of molecular probes to the organellar lumen together with advances in genomic, proteomic, and electrophysiological techniques have led to the identification and characterization of unique pumps, channels, and transporters responsible for the establishment and maintenance of intraorganellar pH. These developments and their implications for cellular function in health and disease are the subject of this review.
{"title":"Determinants, maintenance, and function of organellar pH.","authors":"Spencer A Freeman, Sergio Grinstein, John Orlowski","doi":"10.1152/physrev.00009.2022","DOIUrl":"https://doi.org/10.1152/physrev.00009.2022","url":null,"abstract":"<p><p>The protonation state of soluble and membrane-associated macromolecules dictates their charge, conformation, and functional activity. In addition, protons (H<sup>+</sup> or their equivalents) partake in numerous metabolic reactions and serve as a source of electrochemical energy to drive the transmembrane transport of both organic and inorganic substrates. Stringent regulation of the intracellular pH is therefore paramount to homeostasis. Although the regulation of the cytosolic pH has been studied extensively, our understanding of the determinants of the H<sup>+</sup> concentration ([H<sup>+</sup>]) of intracellular organelles has developed more slowly, limited by their small size and inaccessibility. Recently, however, targeting of molecular probes to the organellar lumen together with advances in genomic, proteomic, and electrophysiological techniques have led to the identification and characterization of unique pumps, channels, and transporters responsible for the establishment and maintenance of intraorganellar pH. These developments and their implications for cellular function in health and disease are the subject of this review.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":null,"pages":null},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40424777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01Epub Date: 2022-05-30DOI: 10.1152/physrev.00015.2022
Faidon Magkos, Dominic N Reeds, Bettina Mittendorfer
In this paper, we provide an overview of the evolution of the definition of hyperglycemia during the past century and the alterations in glucose dynamics that cause fasting and postprandial hyperglycemia. We discuss how extensive mechanistic, physiological research into the factors and pathways that regulate the appearance of glucose in the circulation and its uptake and metabolism by tissues and organs has contributed knowledge that has advanced our understanding of different types of hyperglycemia, namely prediabetes and diabetes and their subtypes (impaired fasting plasma glucose, impaired glucose tolerance, combined impaired fasting plasma glucose, impaired glucose tolerance, type 1 diabetes, type 2 diabetes, gestational diabetes mellitus), their relationships with medical complications, and how to prevent and treat hyperglycemia.
{"title":"Evolution of the diagnostic value of \"the sugar of the blood\": hitting the sweet spot to identify alterations in glucose dynamics.","authors":"Faidon Magkos, Dominic N Reeds, Bettina Mittendorfer","doi":"10.1152/physrev.00015.2022","DOIUrl":"10.1152/physrev.00015.2022","url":null,"abstract":"<p><p>In this paper, we provide an overview of the evolution of the definition of hyperglycemia during the past century and the alterations in glucose dynamics that cause fasting and postprandial hyperglycemia. We discuss how extensive mechanistic, physiological research into the factors and pathways that regulate the appearance of glucose in the circulation and its uptake and metabolism by tissues and organs has contributed knowledge that has advanced our understanding of different types of hyperglycemia, namely prediabetes and diabetes and their subtypes (impaired fasting plasma glucose, impaired glucose tolerance, combined impaired fasting plasma glucose, impaired glucose tolerance, type 1 diabetes, type 2 diabetes, gestational diabetes mellitus), their relationships with medical complications, and how to prevent and treat hyperglycemia.</p>","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":null,"pages":null},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10741208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-01-01DOI: 10.1152/physrev.00038.2019_COR
{"title":"Corrigendum for Davis et al., volume 101, 2020, p. 319-352.","authors":"","doi":"10.1152/physrev.00038.2019_COR","DOIUrl":"https://doi.org/10.1152/physrev.00038.2019_COR","url":null,"abstract":"","PeriodicalId":20193,"journal":{"name":"Physiological reviews","volume":null,"pages":null},"PeriodicalIF":33.6,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33512561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}