1-29-16 Large-scale mitochondrial DNA deletions in patients with CPEO syndrome in Taiwan

Wang, Edward K.; Kao, Ko-Pei; Hsieh, Rong Hong; Lu, Ching-You; Pang, Cheng‐Yoong; Wei, Yau‐Huei

doi:10.1016/s0022-510x(97)85036-8

Cited by 1 publication

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Large‐scale deletions of mtDNA have been reported to be associated with about 60% of the patients with the KSS and CPEO syndromes 8,19. However, it has remained unclear as to how these mtDNA mutations are involved in the pathogenesis of mitochondrial myopathies and encephalomyopathies.…”

Section: Discussionmentioning

confidence: 99%

“…It has been established that a number of neuromuscular diseases are associated with or caused by mitochondrial DNA (mtDNA) mutations 1–7. Among them, large‐scale deletions are frequently seen in the affected tissues of the patients with mitochondrial myopathies such as chronic progressive external ophthalmoplegia (CPEO) and Kearns‐Sayre syndrome 1,6–8. Abundant evidence have been accumulated to suggest that mtDNA deletions affect the expression of genes in the mitochondrial genome,9–12 which in turn elicit defects in the respiratory chain.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increases of Mitochondrial Mass and Mitochondrial Genome in Association with Enhanced Oxidative Stress in Human Cells Harboring 4,977 BP‐Deleted Mitochondrial DNA

Wei¹,

Lee²,

Shing³

et al. 2001

Annals of the New York Academy of Sciences

Self Cite

104

View full text Add to dashboard Cite

In order to investigate the effect of aging-and disease-associated deletion of mtDNA on cellular functions, we used cytoplasm fusion to construct a series of the cybrids harboring varying proportions of mtDNA with 4,977 bp deletion from skin fibroblasts of a patient with chronic progressive external ophthalmoplegia. The cybrids were grown in the Dulbecco's modified Eagle medium supplemented with 5% fetal bovine serum, 100 g/ml pyruvate and 50 g/ml uridine. The population doubling time was longer for the cybrids containing higher proportions of 4,977 bp-deleted mtDNA. In addition, we found that the respiratory function was decreased with the increase of mtDNA with 4,977 bp deletion in the cybrids. Since impairment of the respiratory system of mitochondria increases the electron leak of the respiratory chain, we further determined the oxidative stress in these cybrids. The results showed that the specific contents of 8-hydroxy 2-deoxyguanosine and lipid peroxides of the cybrids harboring > 65% of the 4,977 bp-deleted mtDNA were significantly increased as compared with those of the cybrids containing undetectable mutant mtDNA. On the other hand, we found that the mitochondrial mass and the relative content of the mitochondrial genome in the cybrids harboring 4,977 bpdeleted mtDNA were higher than those of the cybrids containing only wild type mtDNA. The relative content of mtDNA was increased 17% and 30%, respectively, in the cybrids harboring 17% and 56% of mtDNA with 4,977 bp deletion. Moreover, both mitochondrial mass and mtDNA content were concurrently increased by treatment of the cybrids with 180 M of hydrogen peroxide. Taken these findings together, we conclude that increase of mitochondrial mass and mtDNA are the molecular events associated with enhanced oxidative stress in human cells with impaired respiratory function caused by mtDNA deletion.

show abstract

Section: Discussionmentioning

confidence: 99%