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Chapter 35 - Mitochondrial Hepatopathies

from Section IV - Metabolic Liver Disease

Published online by Cambridge University Press:  19 January 2021

By
Austin Larson  and
Ronald J. Sokol
Edited by
Frederick J. Suchy ,
Ronald J. Sokol  and
William F. Balistreri
Edited in association with
Jorge A. Bezerra ,
Cara L. Mack  and
Benjamin L. Shneider
Frederick J. Suchy
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Ronald J. Sokol
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
William F. Balistreri
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Jorge A. Bezerra
Affiliation:
Cincinnati Children’s Hospital Medical Center, Cincinnati
Cara L. Mack
Affiliation:
University of Colorado, Children’s Hospital Colorado, Aurora
Benjamin L. Shneider
Affiliation:
Texas Children’s Hospital, Houston
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Summary

Pathologies of mitochondrial structure and function are now recognized as the etiology of a growing list of monogenic mitochondrial disorders as well as contributing to many common diseases. Studying patients with respiratory chain disorders has contributed much to our current knowledge about mitochondrial biology [1]. Mutations impacting mitochondrial proteins as well as ribosomal and transfer RNAs (tRNAs) are the underlying cause of diseases affecting the nervous system, skeletal and cardiac muscle, the liver, bone marrow, the endocrine and exocrine pancreas, kidney, inner ear and small and large intestines (Table 35.1) [1]. Perturbations in mitochondrial function result in defective oxidative phosphorylation (OXPHOS) and ATP generation, increased generation of reactive oxygen species (ROS), accumulation of hepatocytic lipid, impairment of other mitochondria-based metabolic processes and activation of apoptotic, autophagic and necrotic cell death pathways [2]. The spectrum of genetic etiologies of inherited mitochondrial hepatic and gastrointestinal disorders continues to expand. In addition, mitochondrial dysfunction may be one of the key determinants of hepatocyte survival in other disorders that are not monogenic mitochondrial diseases. Thus, the concept of primary (or genetic) and secondary (or acquired) mitochondrial hepatopathies has developed.

Type
Chapter
Information
Liver Disease in Children , pp. 628 - 652
Publisher: Cambridge University Press
Print publication year: 2021

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