Pub Date : 2024-09-03DOI: 10.1152/physiol.00035.2024
Axel Joly, Arthur Schott, Ira Phadke, Pedro Gonzalez-Menendez, Sandrina Kinet, Naomi Taylor
Hematopoietic stem cells (HSCs) possess the capacity for self-renewal and the sustained production of all mature blood cell lineages. It has been well established that a metabolic rewiring controls the switch of HSCs from a self-renewal state to a more differentiated state but it is only recently that we have appreciated the importance of metabolic pathways in regulating the commitment of progenitors to distinct hematopoietic lineages. In the context of erythroid differentiation, an extensive network of metabolites - including amino acids, sugars, nucleotides, fatty acids, vitamins, and iron - is required for red blood cell (RBC) maturation. In this review, we will highlight the multi-faceted roles via which metabolites regulate physiological erythropoiesis as well as the effects of metabolic perturbations on erythroid lineage commitment and differentiation. Of note, the erythroid differentiation process is associated with an exceptional breadth of SLC metabolite transporter upregulation. Finally, we will discuss how recent research, revealing the critical impact of metabolic reprogramming in diseases of disordered and ineffective erythropoiesis, has created opportunities for the development of novel metabolic-centered therapeutic strategies.
{"title":"Beyond ATP: Metabolite networks as regulators of erythroid differentiation.","authors":"Axel Joly, Arthur Schott, Ira Phadke, Pedro Gonzalez-Menendez, Sandrina Kinet, Naomi Taylor","doi":"10.1152/physiol.00035.2024","DOIUrl":"https://doi.org/10.1152/physiol.00035.2024","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) possess the capacity for self-renewal and the sustained production of all mature blood cell lineages. It has been well established that a metabolic rewiring controls the switch of HSCs from a self-renewal state to a more differentiated state but it is only recently that we have appreciated the importance of metabolic pathways in regulating the commitment of progenitors to distinct hematopoietic lineages. In the context of erythroid differentiation, an extensive network of metabolites - including amino acids, sugars, nucleotides, fatty acids, vitamins, and iron - is required for red blood cell (RBC) maturation. In this review, we will highlight the multi-faceted roles via which metabolites regulate physiological erythropoiesis as well as the effects of metabolic perturbations on erythroid lineage commitment and differentiation. Of note, the erythroid differentiation process is associated with an exceptional breadth of SLC metabolite transporter upregulation. Finally, we will discuss how recent research, revealing the critical impact of metabolic reprogramming in diseases of disordered and ineffective erythropoiesis, has created opportunities for the development of novel metabolic-centered therapeutic strategies.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-05-07DOI: 10.1152/physiol.00014.2024
Enrique Balderas, Sandra H J Lee, Neeraj K Rai, David M Mollinedo, Hannah E Duron, Dipayan Chaudhuri
Oxidative phosphorylation is regulated by mitochondrial calcium (Ca2+) in health and disease. In physiological states, Ca2+ enters via the mitochondrial Ca2+ uniporter and rapidly enhances NADH and ATP production. However, maintaining Ca2+ homeostasis is critical: insufficient Ca2+ impairs stress adaptation, and Ca2+ overload can trigger cell death. In this review, we delve into recent insights further defining the relationship between mitochondrial Ca2+ dynamics and oxidative phosphorylation. Our focus is on how such regulation affects cardiac function in health and disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, mitochondrial cardiomyopathies, Barth syndrome, and Friedreich's ataxia. Several themes emerge from recent data. First, mitochondrial Ca2+ regulation is critical for fuel substrate selection, metabolite import, and matching of ATP supply to demand. Second, mitochondrial Ca2+ regulates both the production and response to reactive oxygen species (ROS), and the balance between its pro- and antioxidant effects is key to how it contributes to physiological and pathological states. Third, Ca2+ exerts localized effects on the electron transport chain (ETC), not through traditional allosteric mechanisms but rather indirectly. These effects hinge on specific transporters, such as the uniporter or the Na+/Ca2+ exchanger, and may not be noticeable acutely, contributing differently to phenotypes depending on whether Ca2+ transporters are acutely or chronically modified. Perturbations in these novel relationships during disease states may either serve as compensatory mechanisms or exacerbate impairments in oxidative phosphorylation. Consequently, targeting mitochondrial Ca2+ holds promise as a therapeutic strategy for a variety of cardiac diseases characterized by contractile failure or arrhythmias.
{"title":"Mitochondrial Calcium Regulation of Cardiac Metabolism in Health and Disease.","authors":"Enrique Balderas, Sandra H J Lee, Neeraj K Rai, David M Mollinedo, Hannah E Duron, Dipayan Chaudhuri","doi":"10.1152/physiol.00014.2024","DOIUrl":"10.1152/physiol.00014.2024","url":null,"abstract":"<p><p>Oxidative phosphorylation is regulated by mitochondrial calcium (Ca<sup>2+</sup>) in health and disease. In physiological states, Ca<sup>2+</sup> enters via the mitochondrial Ca<sup>2+</sup> uniporter and rapidly enhances NADH and ATP production. However, maintaining Ca<sup>2+</sup> homeostasis is critical: insufficient Ca<sup>2+</sup> impairs stress adaptation, and Ca<sup>2+</sup> overload can trigger cell death. In this review, we delve into recent insights further defining the relationship between mitochondrial Ca<sup>2+</sup> dynamics and oxidative phosphorylation. Our focus is on how such regulation affects cardiac function in health and disease, including heart failure, ischemia-reperfusion, arrhythmias, catecholaminergic polymorphic ventricular tachycardia, mitochondrial cardiomyopathies, Barth syndrome, and Friedreich's ataxia. Several themes emerge from recent data. First, mitochondrial Ca<sup>2+</sup> regulation is critical for fuel substrate selection, metabolite import, and matching of ATP supply to demand. Second, mitochondrial Ca<sup>2+</sup> regulates both the production and response to reactive oxygen species (ROS), and the balance between its pro- and antioxidant effects is key to how it contributes to physiological and pathological states. Third, Ca<sup>2+</sup> exerts localized effects on the electron transport chain (ETC), not through traditional allosteric mechanisms but rather indirectly. These effects hinge on specific transporters, such as the uniporter or the Na<sup>+</sup>/Ca<sup>2+</sup> exchanger, and may not be noticeable acutely, contributing differently to phenotypes depending on whether Ca<sup>2+</sup> transporters are acutely or chronically modified. Perturbations in these novel relationships during disease states may either serve as compensatory mechanisms or exacerbate impairments in oxidative phosphorylation. Consequently, targeting mitochondrial Ca<sup>2+</sup> holds promise as a therapeutic strategy for a variety of cardiac diseases characterized by contractile failure or arrhythmias.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-04-30DOI: 10.1152/physiol.00015.2024
Neha Dhyani, Changhai Tian, Lie Gao, Tara L Rudebush, Irving H Zucker
High levels of oxidant stress in the form of reactive oxidant species are prevalent in the circulation and tissues in various types of cardiovascular disease including heart failure, hypertension, peripheral arterial disease, and stroke. Here we review the role of nuclear factor erythroid 2-related factor 2 (Nrf2), an important and widespread antioxidant and anti-inflammatory transcription factor that may contribute to the pathogenesis and maintenance of cardiovascular diseases. We review studies showing that downregulation of Nrf2 exacerbates heart failure, hypertension, and autonomic function. Finally, we discuss the potential for using Nrf2 modulation as a therapeutic strategy for cardiovascular diseases and autonomic dysfunction.
{"title":"Nrf2-Keap1 in Cardiovascular Disease: Which Is the Cart and Which the Horse?","authors":"Neha Dhyani, Changhai Tian, Lie Gao, Tara L Rudebush, Irving H Zucker","doi":"10.1152/physiol.00015.2024","DOIUrl":"10.1152/physiol.00015.2024","url":null,"abstract":"<p><p>High levels of oxidant stress in the form of reactive oxidant species are prevalent in the circulation and tissues in various types of cardiovascular disease including heart failure, hypertension, peripheral arterial disease, and stroke. Here we review the role of nuclear factor erythroid 2-related factor 2 (Nrf2), an important and widespread antioxidant and anti-inflammatory transcription factor that may contribute to the pathogenesis and maintenance of cardiovascular diseases. We review studies showing that downregulation of Nrf2 exacerbates heart failure, hypertension, and autonomic function. Finally, we discuss the potential for using Nrf2 modulation as a therapeutic strategy for cardiovascular diseases and autonomic dysfunction.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-05-07DOI: 10.1152/physiol.00003.2024
Wang-Soo Lee, E Dale Abel, Jaetaek Kim
Insulin-like growth factor-1 (IGF-1) signaling has multiple physiological roles in cellular growth, metabolism, and aging. Myocardial hypertrophy, cell death, senescence, fibrosis, and electrical remodeling are hallmarks of various heart diseases and contribute to the progression of heart failure. This review highlights the critical role of IGF-1 and its cognate receptor in cardiac hypertrophy, aging, and remodeling.
{"title":"New Insights into IGF-1 Signaling in the Heart.","authors":"Wang-Soo Lee, E Dale Abel, Jaetaek Kim","doi":"10.1152/physiol.00003.2024","DOIUrl":"10.1152/physiol.00003.2024","url":null,"abstract":"<p><p>Insulin-like growth factor-1 (IGF-1) signaling has multiple physiological roles in cellular growth, metabolism, and aging. Myocardial hypertrophy, cell death, senescence, fibrosis, and electrical remodeling are hallmarks of various heart diseases and contribute to the progression of heart failure. This review highlights the critical role of IGF-1 and its cognate receptor in cardiac hypertrophy, aging, and remodeling.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-27DOI: 10.1152/physiol.00028.2024
Orlando Laitano, Kentaro Oki, Nisha Charkoudian
Understanding physiological mechanisms of tolerance to heat exposure, and potential ways to improve such tolerance, is increasingly important in the context of ongoing climate change. We discuss the concept of heat tolerance in humans and experimental models (primarily rodents), including intracellular mechanisms and improvements in tolerance with heat acclimation.
{"title":"Factors contributing to heat tolerance in humans & experimental models.","authors":"Orlando Laitano, Kentaro Oki, Nisha Charkoudian","doi":"10.1152/physiol.00028.2024","DOIUrl":"https://doi.org/10.1152/physiol.00028.2024","url":null,"abstract":"<p><p>Understanding physiological mechanisms of tolerance to heat exposure, and potential ways to improve such tolerance, is increasingly important in the context of ongoing climate change. We discuss the concept of heat tolerance in humans and experimental models (primarily rodents), including intracellular mechanisms and improvements in tolerance with heat acclimation.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-27DOI: 10.1152/physiol.00029.2024
Diego Lopez Mateos, Brandon John Harris, Adriana Hernández González, Kush Narang, Vladimir Yarov-Yarovoy
Voltage-gated ion channels (VGICs) are pivotal in regulating electrical activity in excitable cells and are critical pharmaceutical targets for treating many diseases including cardiac arrhythmia and neuropathic pain. Despite their significance, challenges such as achieving target selectivity persist in VGIC drug development. Recent progress in deep learning, particularly diffusion models, has enabled the computational design of protein binders for any clinically relevant protein based solely on its structure. These developments coincide with a surge in experimental structural data for VGICs, providing a rich foundation for computational design efforts. This review explores the recent advancements in computational protein design using deep learning and diffusion methods, focusing on their application in designing protein binders to modulate VGIC activity. We discuss the potential use of these methods to computationally design protein binders targeting different regions of VGICs, including the pore domain, voltage-sensing domains, and interface with auxiliary subunits. We provide a comprehensive overview of the different design scenarios, discuss key structural considerations, and address the practical challenges in developing VGIC-targeting protein binders. By exploring these innovative computational methods, we aim to provide a framework for developing novel strategies that could significantly advance VGIC pharmacology and lead to the discovery of effective and safe therapeutics.
{"title":"Harnessing Deep Learning Methods for Voltage-Gated Ion Channel Drug Discovery.","authors":"Diego Lopez Mateos, Brandon John Harris, Adriana Hernández González, Kush Narang, Vladimir Yarov-Yarovoy","doi":"10.1152/physiol.00029.2024","DOIUrl":"https://doi.org/10.1152/physiol.00029.2024","url":null,"abstract":"<p><p>Voltage-gated ion channels (VGICs) are pivotal in regulating electrical activity in excitable cells and are critical pharmaceutical targets for treating many diseases including cardiac arrhythmia and neuropathic pain. Despite their significance, challenges such as achieving target selectivity persist in VGIC drug development. Recent progress in deep learning, particularly diffusion models, has enabled the computational design of protein binders for any clinically relevant protein based solely on its structure. These developments coincide with a surge in experimental structural data for VGICs, providing a rich foundation for computational design efforts. This review explores the recent advancements in computational protein design using deep learning and diffusion methods, focusing on their application in designing protein binders to modulate VGIC activity. We discuss the potential use of these methods to computationally design protein binders targeting different regions of VGICs, including the pore domain, voltage-sensing domains, and interface with auxiliary subunits. We provide a comprehensive overview of the different design scenarios, discuss key structural considerations, and address the practical challenges in developing VGIC-targeting protein binders. By exploring these innovative computational methods, we aim to provide a framework for developing novel strategies that could significantly advance VGIC pharmacology and lead to the discovery of effective and safe therapeutics.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13DOI: 10.1152/physiol.00024.2024
Daniel H Katz, Malene E Lindholm, Euan A Ashley
Physical activity plays a fundamental role in human health and disease. Exercise has been shown to improve a wide variety of disease states, and the scientific community is committed to understanding the precise molecular mechanisms that underlie the exquisite benefits. This review provides an overview of molecular responses to acute exercise and chronic training, particularly energy mobilization and generation, structural adaptation, inflammation, and immune regulation. Further it offers a detailed discussion on known molecular signals and systemic regulators activated during various forms of exercise and their role in orchestrating health benefits. Critically, the increasing use of multi-omic technologies is explored with an emphasis on how multi-omic and multi-tissue studies contribute to a more profound understanding of exercise biology. These data inform anticipated future advancement in the field and highlight the prospect of integrating exercise with pharmacology for personalized disease prevention and treatment.
{"title":"Charting the Molecular Terrain of Exercise: The Power of Multi-Omic Mapping.","authors":"Daniel H Katz, Malene E Lindholm, Euan A Ashley","doi":"10.1152/physiol.00024.2024","DOIUrl":"https://doi.org/10.1152/physiol.00024.2024","url":null,"abstract":"<p><p>Physical activity plays a fundamental role in human health and disease. Exercise has been shown to improve a wide variety of disease states, and the scientific community is committed to understanding the precise molecular mechanisms that underlie the exquisite benefits. This review provides an overview of molecular responses to acute exercise and chronic training, particularly energy mobilization and generation, structural adaptation, inflammation, and immune regulation. Further it offers a detailed discussion on known molecular signals and systemic regulators activated during various forms of exercise and their role in orchestrating health benefits. Critically, the increasing use of multi-omic technologies is explored with an emphasis on how multi-omic and multi-tissue studies contribute to a more profound understanding of exercise biology. These data inform anticipated future advancement in the field and highlight the prospect of integrating exercise with pharmacology for personalized disease prevention and treatment.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1152/physiol.00027.2024
Giulia Soggia, Yasmin ElMaghloob, Annie-Kermen Boromangnaeva, Adel Al Jord
Organism health relies on cell proliferation, migration, and differentiation. These universal processes depend on cytoplasmic reorganization driven notably by the cytoskeleton and its force-generating motors. Their activity generates forces that mechanically agitate the cell nucleus and its interior. New evidence from reproductive cell biology revealed that these cytoskeletal forces can be tuned to remodel nuclear membrane-less compartments, known as biomolecular condensates, and regulate their RNA processing function for the success of subsequent cell division that is critical for fertility. Both cytoskeletal and nuclear condensate reorganization are common to numerous physiological and pathological contexts, raising the possibility that mechanical remodeling of nuclear condensates may be a much broader mechanism regulating their function. Here, we review this newfound mechanism of condensate remodeling and venture into contexts of health and disease where it may be relevant, with a focus on reproduction, cancer, and premature aging.
{"title":"Mechanical remodeling of nuclear biomolecular condensates.","authors":"Giulia Soggia, Yasmin ElMaghloob, Annie-Kermen Boromangnaeva, Adel Al Jord","doi":"10.1152/physiol.00027.2024","DOIUrl":"10.1152/physiol.00027.2024","url":null,"abstract":"<p><p>Organism health relies on cell proliferation, migration, and differentiation. These universal processes depend on cytoplasmic reorganization driven notably by the cytoskeleton and its force-generating motors. Their activity generates forces that mechanically agitate the cell nucleus and its interior. New evidence from reproductive cell biology revealed that these cytoskeletal forces can be tuned to remodel nuclear membrane-less compartments, known as biomolecular condensates, and regulate their RNA processing function for the success of subsequent cell division that is critical for fertility. Both cytoskeletal and nuclear condensate reorganization are common to numerous physiological and pathological contexts, raising the possibility that mechanical remodeling of nuclear condensates may be a much broader mechanism regulating their function. Here, we review this newfound mechanism of condensate remodeling and venture into contexts of health and disease where it may be relevant, with a focus on reproduction, cancer, and premature aging.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-06DOI: 10.1152/physiol.00022.2024
Hanah M Georges, Errol R Norwitz, Vikki M Abrahams
Preterm birth remains a worldwide health concern due to ongoing challenges in prediction and prevention. Current predictors are limited by poor performance, need for invasive sampling, and an inability to identify patients in a timely fashion to allow for effective intervention. The multiple etiologies of preterm birth often have an inflammatory component. Thus, a deeper understanding of the inflammatory mechanisms involved in preterm birth may provide opportunities to identify new predictors of preterm birth. This review will discuss the multiple etiologies of preterm birth, their links to inflammation, current predictors available, and new directions for the field.
{"title":"Predictors of Inflammation-Mediated Preterm Birth.","authors":"Hanah M Georges, Errol R Norwitz, Vikki M Abrahams","doi":"10.1152/physiol.00022.2024","DOIUrl":"10.1152/physiol.00022.2024","url":null,"abstract":"<p><p>Preterm birth remains a worldwide health concern due to ongoing challenges in prediction and prevention. Current predictors are limited by poor performance, need for invasive sampling, and an inability to identify patients in a timely fashion to allow for effective intervention. The multiple etiologies of preterm birth often have an inflammatory component. Thus, a deeper understanding of the inflammatory mechanisms involved in preterm birth may provide opportunities to identify new predictors of preterm birth. This review will discuss the multiple etiologies of preterm birth, their links to inflammation, current predictors available, and new directions for the field.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141898670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-30DOI: 10.1152/physiol.00020.2024
Brunna Martins, Jan Mossemann, Fiorelle Aguilar, Sarah Zhao, Philip J Bilan, Blayne Amir Sayed
Liver transplantation has evolved into a mature clinical field but scarcity of usable organs poses a unique challenge. Expanding the donor pool requires novel approaches for protecting hepatic physiology and cellular homeostasis. Here we define hepatocellular injury during transplantation, with an emphasis on modifiable cell death pathways as future therapeutics.
{"title":"Liver transplantation: a test of cellular physiology, preservation and injury.","authors":"Brunna Martins, Jan Mossemann, Fiorelle Aguilar, Sarah Zhao, Philip J Bilan, Blayne Amir Sayed","doi":"10.1152/physiol.00020.2024","DOIUrl":"https://doi.org/10.1152/physiol.00020.2024","url":null,"abstract":"<p><p>Liver transplantation has evolved into a mature clinical field but scarcity of usable organs poses a unique challenge. Expanding the donor pool requires novel approaches for protecting hepatic physiology and cellular homeostasis. Here we define hepatocellular injury during transplantation, with an emphasis on modifiable cell death pathways as future therapeutics.</p>","PeriodicalId":49694,"journal":{"name":"Physiology","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}