Liver autophagy: much more than just taking out the trash

Key Points Autophagy contributes to the maintenance of the energetic balance, participates in hepatocyte quality control and aids in the defence against exogenous pathogens and conditions that cause cellular toxicity in the liver The different autophagic pathways that coexist in the liver are in dyn...

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Published inNature reviews. Gastroenterology & hepatology Vol. 11; no. 3; pp. 187 - 200
Main Authors Schneider, Jaime L., Cuervo, Ana Maria
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.03.2014
Nature Publishing Group
Subjects
692/699/1503/1607/2750
692/699/1503/234/2513
692/699/317
692/699/67/1504/1610
Autophagy
Autophagy (Cytology)
Biomedicine
Carcinogenesis
Gastroenterology
Hepatocytes
Hepatocytes - pathology
Hepatology
Homeostasis
Humans
Liver
Liver - pathology
Liver diseases
Liver Diseases - pathology
Lysosomes
Lysosomes - pathology
Medicine & Public Health
Nutritional status
Organelles
Phagocytosis
Physiological aspects
Physiological research
review-article
Online AccessGet full text

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Abstract Key Points Autophagy contributes to the maintenance of the energetic balance, participates in hepatocyte quality control and aids in the defence against exogenous pathogens and conditions that cause cellular toxicity in the liver The different autophagic pathways that coexist in the liver are in dynamic intercommunication with one another, enabling a coordinated response to maintain homeostasis Failure to properly execute the autophagic program leaves hepatocytes vulnerable to stressors and unable to accommodate the extreme energetic demands of this organ Autophagy malfunction underlies the pathogenesis of common liver diseases, including metabolic disorders, protein conformational diseases, viral infection and carcinogenesis Chemical modulation of autophagy has proven to be beneficial in certain liver pathologies, although manipulation of autophagy needs to be customized according to the status of the autophagic pathway in each disease state In this Review—intended as an introduction to the topic of hepatic autophagy for clinical scientists—the authors describe the different types of hepatic autophagy, their role in maintaining homeostasis in a healthy liver and the contribution of autophagic malfunction to liver disease. Studies performed in the liver in the 1960s led to the identification of lysosomes and the discovery of autophagy, the process by which intracellular proteins and organelles are degraded in lysosomes. Early studies in hepatocytes also uncovered how nutritional status regulates autophagy and how various circulating hormones modulate the activity of this catabolic process in the liver. The intensive characterization of hepatic autophagy over the years has revealed that lysosome-mediated degradation is important not only for maintaining liver homeostasis in normal physiological conditions, but also for an adequate response of this organ to stressors such as proteotoxicity, metabolic dysregulation, infection and carcinogenesis. Autophagic malfunction has also been implicated in the pathogenesis of common liver diseases, suggesting that chemical manipulation of this process might hold potential therapeutic value. In this Review—intended as an introduction to the topic of hepatic autophagy for clinical scientists—we describe the different types of hepatic autophagy, their role in maintaining homeostasis in a healthy liver and the contribution of autophagic malfunction to liver disease.
AbstractList Studies performed in the liver in the 1960s led to the identification of lysosomes and the discovery of autophagy, the process by which intracellular proteins and organelles are degraded in lysosomes. Early studies in hepatocytes also uncovered how nutritional status regulates autophagy and how various circulating hormones modulate the activity of this catabolic process in the liver. The intensive characterization of hepatic autophagy over the years has revealed that lysosome-mediated degradation is important not only for maintaining liver homeostasis in normal physiological conditions, but also for an adequate response of this organ to stressors such as proteotoxicity, metabolic dysregulation, infection and carcinogenesis. Autophagic malfunction has also been implicated in the pathogenesis of common liver diseases, suggesting that chemical manipulation of this process might hold potential therapeutic value. In this Review--intended as an introduction to the topic of hepatic autophagy for clinical scientists--we describe the different types of hepatic autophagy, their role in maintaining homeostasis in a healthy liver and the contribution of autophagic malfunction to liver disease.
Key Points Autophagy contributes to the maintenance of the energetic balance, participates in hepatocyte quality control and aids in the defence against exogenous pathogens and conditions that cause cellular toxicity in the liver The different autophagic pathways that coexist in the liver are in dynamic intercommunication with one another, enabling a coordinated response to maintain homeostasis Failure to properly execute the autophagic program leaves hepatocytes vulnerable to stressors and unable to accommodate the extreme energetic demands of this organ Autophagy malfunction underlies the pathogenesis of common liver diseases, including metabolic disorders, protein conformational diseases, viral infection and carcinogenesis Chemical modulation of autophagy has proven to be beneficial in certain liver pathologies, although manipulation of autophagy needs to be customized according to the status of the autophagic pathway in each disease state In this Review—intended as an introduction to the topic of hepatic autophagy for clinical scientists—the authors describe the different types of hepatic autophagy, their role in maintaining homeostasis in a healthy liver and the contribution of autophagic malfunction to liver disease. Studies performed in the liver in the 1960s led to the identification of lysosomes and the discovery of autophagy, the process by which intracellular proteins and organelles are degraded in lysosomes. Early studies in hepatocytes also uncovered how nutritional status regulates autophagy and how various circulating hormones modulate the activity of this catabolic process in the liver. The intensive characterization of hepatic autophagy over the years has revealed that lysosome-mediated degradation is important not only for maintaining liver homeostasis in normal physiological conditions, but also for an adequate response of this organ to stressors such as proteotoxicity, metabolic dysregulation, infection and carcinogenesis. Autophagic malfunction has also been implicated in the pathogenesis of common liver diseases, suggesting that chemical manipulation of this process might hold potential therapeutic value. In this Review—intended as an introduction to the topic of hepatic autophagy for clinical scientists—we describe the different types of hepatic autophagy, their role in maintaining homeostasis in a healthy liver and the contribution of autophagic malfunction to liver disease.
Studies performed in the liver in the 1960s led to the identification of lysosomes and the discovery of autophagy, the process by which intracellular proteins and organelles are degraded in lysosomes. Early studies in hepatocytes also uncovered how nutritional status regulates autophagy and how various circulating hormones modulate the activity of this catabolic process in the liver. The intensive characterization of hepatic autophagy over the years has revealed that lysosome-mediated degradation is important not only for maintaining liver homeostasis in normal physiological conditions, but also for an adequate response of this organ to stressors such as proteotoxicity, metabolic dysregulation, infection and carcinogenesis. Autophagic malfunction has also been implicated in the pathogenesis of common liver diseases, suggesting that chemical manipulation of this process might hold potential therapeutic value. In this Review--intended as an introduction to the topic of hepatic autophagy for clinical scientists--we describe the different types of hepatic autophagy, their role in maintaining homeostasis in a healthy liver and the contribution of autophagic malfunction to liver disease. Schneider, J. L. & Cuervo, A. M. Nat. Rev. Gastroenterol. Hepatol. 11, 187-200 (2014); published online 5 November 2013; doi: 10.1038/nrgastro.2013.211
Studies performed in the liver in the 1960s led to the identification of lysosomes and the discovery of autophagy, the process by which intracellular proteins and organelles are degraded in lysosomes. Early studies in hepatocytes also uncovered how nutritional status regulates autophagy and how various circulating hormones modulate the activity of this catabolic process in the liver. The intensive characterization of hepatic autophagy over the years has revealed that lysosome-mediated degradation is important not only for maintaining liver homeostasis in normal physiological conditions, but also for an adequate response of this organ to stressors such as proteotoxicity, metabolic dysregulation, infection and carcinogenesis. Autophagic malfunction has also been implicated in the pathogenesis of common liver diseases, suggesting that chemical manipulation of this process might hold potential therapeutic value. In this Review—intended as an introduction to the topic of hepatic autophagy for clinical scientists—we describe the different types of hepatic autophagy, their role in maintaining homeostasis in a healthy liver and the contribution of autophagy malfunction to liver disease.
Audience Academic
Author Cuervo, Ana Maria
Schneider, Jaime L.
Author_xml – sequence: 1
  givenname: Jaime L.
  surname: Schneider
  fullname: Schneider, Jaime L.
  organization: Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine
– sequence: 2
  givenname: Ana Maria
  surname: Cuervo
  fullname: Cuervo, Ana Maria
  email: ana-maria.cuervo@einstein.yu.edu
  organization: Department of Developmental and Molecular Biology, Institute for Aging Studies, Albert Einstein College of Medicine
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Snippet Key Points Autophagy contributes to the maintenance of the energetic balance, participates in hepatocyte quality control and aids in the defence against...
Studies performed in the liver in the 1960s led to the identification of lysosomes and the discovery of autophagy, the process by which intracellular proteins...
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SubjectTerms 692/699/1503/1607/2750
692/699/1503/234/2513
692/699/317
692/699/67/1504/1610
Autophagy
Autophagy (Cytology)
Biomedicine
Carcinogenesis
Gastroenterology
Hepatocytes
Hepatocytes - pathology
Hepatology
Homeostasis
Humans
Liver
Liver - pathology
Liver diseases
Liver Diseases - pathology
Lysosomes
Lysosomes - pathology
Medicine & Public Health
Nutritional status
Organelles
Phagocytosis
Physiological aspects
Physiological research
review-article
Title Liver autophagy: much more than just taking out the trash
URI https://link.springer.com/article/10.1038/nrgastro.2013.211
https://www.ncbi.nlm.nih.gov/pubmed/24192609
https://www.proquest.com/docview/1787864374
https://pubmed.ncbi.nlm.nih.gov/PMC3980679
Volume 11
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