Mitochondrial Medicine

A Primer for Health Care Providers and Translational Researchers

Pankaj Prasun

• Publisher: Academic Press
• Year: 2019
• Print ISBN: 9780128170069
• eBook ISBN: 9780128170076
• Topic: Medicine
• Subtopic: Genetics in Medicine

Mitochondrial Medicine: A Primer for Health Care Providers and Translational Researchers is an applied, holistic resource that addresses the evolving and multidisciplinary area of mitochondrial disease. The book discusses the fundamentals of mitochondrial medicine in humans, as well as the pathophysiology, diagnosis and treatment of mitochondrial diseases. Three all-inclusive sections examine the role of mitochondria in common medical conditions, such as diabetes, heart failure and the full range of inherited mitochondrial diseases. Sections cover the genetic and biochemical basis of both mitochondrial DNA deletion syndromes and point mutation syndromes, their clinical presentation, treatment plans, genetic counseling, prenatal testing, and ongoing research. While providing a solid foundation in its topic area, each chapter in the book is written in an accessible format with illustrative case studies, thus making it a quick bedside or clinical laboratory reference. - Includes a basic introduction to mitochondria and their misfunctions in human disease - Presents current practice and research in mitochondrial medicine, with an emphasis on clinical presentation, diagnosis, treatment, genetic counseling and prenatal testing - Features short, accessible chapters with illustrative case studies for quick reference - Provides thorough coverage of inherited mitochondrial disorders, as well as the role of mitochondria in common medical conditions

Section II

Inherited Mitochondrial Diseases

Outline

Chapter 8. Mitochondrial Diseases: Classification

Chapter 9. Mitochondrial DNA Deletion Disorders

Chapter 10. Mitochondrial DNA Point Mutation Disorders

Chapter 11. Mitochondrial Disease of Nuclear Origin: Respiratory Chain Complex Units

Chapter 12. Mitochondrial Disease of Nuclear Origin: Disorders of Mitochondrial DNA Replication

Chapter 13. Mitochondrial Disease of Nuclear Origin: Disorders of Mitochondrial DNA Transcription and Translation

Chapter 14. Mitochondrial Disease of Nuclear Origin: Disorders of Mitochondrial Homeostasis

Chapter 15. Disorders of Pyruvate Metabolism and Tricarboxylic Acid Cycle

Chapter 8

Mitochondrial Diseases

Classification

Abstract

Mitochondrial genetic material is incomplete. Approximately 1500 proteins encoded by nuclear genes are required for mitochondrial biogenesis and function. Mitochondrial diseases can be broadly classified as due to mitochondrial DNA mutations or nuclear DNA mutations. Those caused by nuclear DNA mutations can further be classified based on whether they affect respiratory chain unit formation, mitochondrial DNA maintenance, transcription, translation, or mitochondrial homeostasis. In addition, tricarboxylic acid cycle and pyruvate metabolism disorders closely resemble mitochondrial diseases and hence often discussed with mitochondrial diseases.

Keywords

Classification; Genetics; Mitochondrial disease; Mitochondrial DNA; Nuclear gene

Introduction

Mitochondrial disease can be caused by a mutation in either mitochondrial or nuclear DNA. Mitochondrial genetic material is incomplete. Nuclear genes are required for mitochondrial biogenesis and mitochondrial functions. Approximately 1500 proteins encoded by nuclear genes are required for mitochondrial function. Mitochondrial diseases can be broadly classified as due to mitochondrial DNA mutations and nuclear DNA mutations.

Mitochondrial Diseases Caused by Mitochondrial DNA Mutations

Mitochondrial DNA diseases can be divided into diseases caused by mtDNA rearrangements (such as deletion) and mtDNA point mutations. Mitochondrial DNA point mutations can lead to the impaired synthesis of individual respiratory chain subunit or impairment of mitochondrial protein synthesis machinery (Table 8.1).

Mitochondrial Diseases Caused by Nuclear Gene Mutations

Approximately 300 nuclear genes have been associated with mitochondrial diseases. Nuclear gene defects can cause mitochondrial disease by several mechanisms such as impairment of respiratory complex subunit synthesis, respiratory complex assembly, mitochondrial DNA replication, mitochondrial DNA translation, or mitochondrial homeostasis (Table 8.2). In addition, disorders of tricarboxylic acid cycle and pyruvate metabolism are often classified under mitochondrial diseases.

Table 8.1

Mitochondrial Diseases Caused by mtDNA Mutations

Mitochondrial DNA Rearrangement		Example
Mitochondrial DNA deletion		Kearns-Sayre syndrome
		Pearson syndrome
		Chronic progressive external ophthalmoplegia (CPEO)
Mitochondrial DNA Point Mutation		Example
Mutations in genes encoding respiratory chain subunit		Leber heredita...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Preface
• About This Book
• Abbreviation List
• Notice
• Section I. Basics of Mitochondrial Medicine
• Section II. Inherited Mitochondrial Diseases
• Section III. Mitochondria and Common Medical Conditions
• Useful Websites
• Commonly Prescribed Mitochondrial Supplements
• Index