Structural and functional mitochondrial abnormalities associated with high levels of partially deleted mitochondrial DNAs in somatic cell hybrids
- 1 September 1992
- journal article
- research article
- Published by Springer Nature in Somatic Cell and Molecular Genetics
- Vol. 18 (5) , 431-442
- https://doi.org/10.1007/bf01233083
Abstract
Kearns-Sayre syndrome (KSS) is a progressive and ultimately fatal human encephalomyopathy that is associated with large-scale deletions of mitochondrial DNA (mtDNA). To gain new insights into the developmental pathobiology of this disease, we studied the maintenance and expression of deleted mtDNAs (Δ-mtDNAs) in somatic cell hybrids generated by fusion of HeLacot cells with a KSS fibroblast clone containing both wild-type and Δ-mtDNAs. We observed that Δ-mtDNAs were preferentially maintained over the KSS wild-type mtDNAs (wt-mtDNAs) in almost all isolated hybrid clones. Mitochondrial metabolism was not compromised in hybrids containing as much as 70–79% Δ-mtDNAs. Two clones containing more than 99% Δ-mtDNA were severely deficient in oxidative phosphorylation and exhibited abnormal, enlarged mitochondria. These clones had undetectable levels of mtDNA-encoded polypeptides, but contained normal amounts of a nuclear DNA-encoded mitochondrial protein. The data suggest a nonrandom pattern of mtDNA segregation in the triplasmic hybrids and a correlation among Δ-mtDNA, structural mitochondrial abnormalities, and mitochondrial dysfunction.Keywords
This publication has 28 references indexed in Scilit:
- Introduction of disease-related mitochondrial DNA deletions into HeLa cells lacking mitochondrial DNA results in mitochondrial dysfunction.Proceedings of the National Academy of Sciences, 1991
- Chronic progressive external ophthalmoplegia: A correlative study of mitochondrial DNA deletions and their phenotypic expression in muscle biopsiesJournal of the Neurological Sciences, 1990
- Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy.Journal of Clinical Investigation, 1990
- Recombination via flanking direct repeats is a major cause of large-scale deletions of human mitochondrial DNANucleic Acids Research, 1990
- Mitochondrial myopathies: Clinical and biochemical features of 30 patients with major deletions of muscle mitochondrial DNAAnnals of Neurology, 1989
- Spontaneous Kearns-Sayre/chronic external ophthalmoplegia plus syndrome associated with a mitochondrial DNA deletion: a slip-replication model and metabolic therapy.Proceedings of the National Academy of Sciences, 1989
- Mitochondrial DNA Deletions in Progressive External Ophthalmoplegia and Kearns-Sayre SyndromeNew England Journal of Medicine, 1989
- A Direct Repeat Is a Hotspot for Large-Scale Deletion of Human Mitochondrial DNAScience, 1989
- Deletions of mitochondrial DNA in Kearns‐Sayre syndromeNeurology, 1988
- Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathiesNature, 1988