MOLECULAR GENETIC ASPECTS OF HUMAN MITOCHONDRIAL DISORDERS
Abstract
This review focuses on mutations of mitochondrial DNA (mtDNA) which are an important cause of mitochondrial disorders in humans and are also associated with common neurodegenerative disorders and aging. The high copy number of mtDNA and its maternal transmission make the inheritance of mtDNA mutations fundamentally different from the Mendelian inheritance of nuclear DNA mutations. There is often a mixture of wild-type and mutated mtDNAs (heteroplasmy), and heterogeneity in the distribution of mutated mtDNAs is one plausible explanation for the widely varying phenotypes in patients with mitochondrial disorders. The application of molecular genetics has led to significant progress in the studies of human mitochondrial disorders in the past decade. Future studies including the development of animal models are needed to advance our understanding of the pathogenesis of mitochondrial disorders to enable, in tum, the development of novel therapies and genetic rescue strategies for the treatment of human disease.
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The tissue-specific knockout animals reproduce important pathophysiological features found in human patients with mitochondrial myopathy, i.e., RRFs with COX deficiency, accumulation of abnormally appearing mitochondria, and progressively deteriorating respiratory chain function in skeletal muscle.
“These tissue-specific knockout animals reproduce important pathophysiological features found in human patients with mitochondrial myopathy, i.e., RRFs with COX deficiency (1), accumulation of abnormally appearing mitochondria (23), and progressively deteriorating respiratory chain function in skeletal muscle (24,25).”
From Increased mitochondrial mass in mitochondrial myopathy mice (2002) · cites this paper as [1]
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Self-citation
- Authors
- Larsson, N.-G., & Clayton, D. A.
- Affiliations
- Stanford Medicine (US)
- ORCID
- Larsson, Nils-Göran
- Venue
- Annual Review of Genetics
- Publisher
- Annual Reviews
- Published
- 1995-12
- Volume
- 29
- Issue
- 1
- Pages
- 151-178
- ISSN
- 0066-4197 (ISSN-L)
- 1545-2948
- OpenAlex
- W2162288115
- Cited by
- 493
- References
- 53
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 5 · 2023: 7 · 2022: 14 · 2021: 6 · 2020: 16 · 2019: 11 · 2018: 7 · 2017: 12 · 2016: 10 · 2015: 15 · 2014: 10 · 2013: 12 · 2012: 12
- FWCI
- 7.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5r37gm033088-25)
- National Institute of General Medical Sciences (R37 GM-33088)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- mitochondrial DNA mutations, mitochondrial disease, heteroplasmy, maternal inheritance, neurodegenerative diseases, aging, animal models, genetic rescue, mitochondrial disease therapy
- MeSH terms
- Animals, Cell Nucleus, DNA, Mitochondrial, Electron Transport, Multigene Family, Genetics, Medical, Humans, Mutation, Proteins, RNA, Transfer, Genome, Human, Gene Deletion
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