Mitochondrial Diseases

This collection of reviews and protocols provides the reader with an introduction to the current state of knowledge on how various diseases are related to mitochondrial dysfunction. Mitochondria contain their own genome, a small, circular double-stranded DNA (mtDNA), and alterations in mtDNA may play an important role in the multistep carcinogenesis of at least some types of human cancer. In addition to mutations of mtDNA, many mitochondrial syndromes are due to abnormalities in nuclear genes related to oxidative phosphorylation (OXPHOS). Mitochondrial tRNA (MTT) gene mutations are an important cause of human morbidity and are associated with a wide range of pathology, from isolated organ?]specific diseases such as myopathy or hearing loss, to multisystem disorders with encephalopathy, gastrointestinal dysmotility, and life?]threatening cardiomyopathy. The relationship of the mitochondrion organelle to aging and longevity is also discussed.

Laboratory protocols describe methodology to characterize mtDNA heteroplasmy by parallel sequencing. Each eukaryotic cell contains hundreds of mitochondria with hundreds of mitochondria genomes. Mutant and wild-type mtDNA may co-exist as heteroplasmy, and cause human disease. The purpose of this protocol is to simultaneously determine mtDNA sequence and quantify the heteroplasmic level. Another protocol describes procedures for obtaining tissue sections and cell material suitable for histological evaluation of OXPHOS activity and integrity and immunodetection of the complexes in tissue from patients suspected of mitochondrial disease. Emphasis lies on the diagnostic potential of these techniques to differentiate mtDNA from nuclear mutations.

This e-book — a curated collection from eLS, WIREs, and Current Protocols — offers a fantastic introduction to the field of mitochondrial diseases for students or interdisciplinary collaborators.

Table of Contents:

Introduction

Mitochondrial DNA Copy Number Alterations in Human Cancers
eLS
Man Yu

Mitochondrial Disorders: Nuclear Gene Mutations
eLS
Daniele Ghezzi and Massimo Zeviani

Mitochondria as a Key Determinant of Aging
eLS
Ludivine Walter and Siu Sylvia Lee

Advanced Reviews

Mitochondrial tRNA Mutations and Disease
WIREs RNA
John W. Yarham, Joanna L. Elson, Emma L. Blakely, Robert McFarland, Robert W. Taylor

Human Mitochondrial Diseases Caused by Lack of Taurine Modification in Mitochondrial tRNAs
WIREs RNA
Suzuki Tsutomu, Nagao Asuteka, Suzuki Takeo

Protocols

Next Generation Sequencing to Characterize Mitochondrial Genomic DNA Heteroplasmy
Current Protocols in Human Genetics
Taosheng Huang

Histochemical Methods for the Diagnosis of Mitochondrial Diseases
Current Protocols in Human Genetics
Boel De Paepe, Jan L. De Bleecker, Rudy Van Coster