Disorders of the mitochondrial respiratory chain

doi:10.1017/CBO9780511544873.063

62 - Disorders of the mitochondrial respiratory chain

from Part X - Other neurodegenerative diseases

Published online by Cambridge University Press: 04 August 2010

M. Flint Beal ,

Anthony E. Lang and

Albert C. Ludolph

Anthony H. V. Schapira

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M. Flint Beal: Affiliation:
Cornell University, New York
Anthony E. Lang: Affiliation:
University of Toronto
Albert C. Ludolph: Affiliation:
Universität Ulm, Germany
Anthony H. V. Schapira: Affiliation:
Royal Free and University College Medical School, and Institute of Neurology, University College London, UK

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Summary

Introduction

Mitochondria are ubiquitous and present in all mammalian cells. They are host to a range of biochemical pathways including oxidative phosphorylation, β-oxidation and the urea cycle. Mitochondria are also important in mediating a variety of intracellular triggers for apoptotic cell death. This chapter will focus on defects of the mitochondrial respiratory chain and specifically those that are related to human diseases; toxin induced mitochondrial defects will be considered elsewhere.

The mitochondrial respiratory chain and oxidative phosphorylation system comprises five multisubunit proteins, which are embedded within the inner mitochondrial membrane. The first four complexes are connected in functional terms by coenzyme Q, and cytochrome c. Electrons are transferred from NADH and FADH2 and result in the reduction of oxygen to water. This process also involves the shuttling of protons across the inner membrane to the internal membranous space, and this provides the proton motive force for the generation of ATP from ADP by complex V (ATPase).

Complexes I–V comprise approximately 82 different subunits, of which 13 are encoded by mitochondrial DNA. The remainder are encoded by nuclear genes and imported into the mitochondrium often by way of specific targeting sequences and import machinery. Mitochondrial DNA is a 16.5 kb double-stranded circular molecule, which lies in the matrix attached near its D-loop to the inner mitochondrial membrane. Mitochondrial DNA encodes 2 ribosomal RNAs, 22 transfer RNAs and 13 proteins (Table 62.1 and Fig. 62.1). It is dependent upon nuclear enzymes for transcription, translation, replication and repair.

Type: Chapter
Information: Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
, pp. 909 - 926

DOI: https://doi.org/10.1017/CBO9780511544873.063 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

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62 - Disorders of the mitochondrial respiratory chain

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