Mitochondrial defects in cardiomyopathy and neuromuscular disease.

Abstract:

:Over the past 11 years, a considerable body of evidence has accumulated implicating defects in the mitochondrial energy-generating pathway, oxidative phosphorylation, in a wide variety of degenerative diseases including myopathy and cardiomyopathy. Most classes of pathogenic mitochondrial DNA mutations affect the heart, in association with a variety of other clinical manifestations that can include skeletal muscle, the central nervous system (including eye), the endocrine system, and the renal system. To better understand the pathophysiologic basis of mitochondrial diseases and their role in myopathy and cardiomyopathy, several mouse models of mitochondrial disease have been prepared. Mitochondrial DNA mutations from cultured cells have been introduced into mice; nuclear DNA genes involved in mitochondrial energy production and reactive oxygen species detoxification have been genetically inactivated, which resulted in mice with hypertrophic and dilated cardiomyopathy, respectively. Physiologic characterization of these mice has confirmed the importance of decreased mitochondrial energy production, increased mitochondrial reactive oxygen species production, and the mitochondrial initiation of apoptosis in mitochondrial disease. With these insights, new therapeutic approaches for neuromuscular and cardiac disease have been suggested.

journal_name

Am Heart J

journal_title

American heart journal

authors

Wallace DC

doi

10.1067/mhj.2000.103934

subject

Has Abstract

pub_date

2000-02-01 00:00:00

pages

S70-85

issue

2 Pt 3

eissn

0002-8703

issn

1097-6744

pii

S0002-8703(00)12744-9

journal_volume

139

pub_type

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