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Attenuation of UV‐Induced Apoptosis by Coenzyme Q 10 in Human Cells Harboring Large‐Scale Deletion of Mitochondrial DNA
Author(s) -
LEE CHENGFENG,
LIU CHUNYI,
CHEN SHUMEI,
SIKORSKA MARIANNA,
LIN CHENYU,
CHEN TZULING,
WEI YAUHUEI
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1338.036
Subject(s) - mitochondrial dna , coenzyme q10 , mitochondrion , apoptosis , microbiology and biotechnology , biology , dna fragmentation , coenzyme q – cytochrome c reductase , programmed cell death , dna damage , cytochrome c , fragmentation (computing) , apoptosis inducing factor , reactive oxygen species , dna , genetics , caspase , biochemistry , gene , ecology
A bstract : Chronic progressive external ophthalmoplegia (CPEO) syndrome is one of the mitochondrial diseases caused by large‐scale deletions in mitochondrial DNA (mtDNA) that impair the respiratory function of mitochondria and result in decreased production of ATP in affected tissues. In order to investigate whether CPEO‐associated mtDNA mutations (i.e., 4,366‐bp and 4,977‐ bp large‐scale deletions) render human cells more vulnerable to apoptosis, we constructed cybrids carrying the deleted mtDNA. Assays for cell viability, DNA fragmentation, cytochrome c release, and caspase 3 activation revealed that UV irradiation at 20 J/m 2 triggered apoptosis in all the cybrids. This treatment also produced elevated intracellular levels of reactive oxygen species (ROS). The rate of UV‐induced cell death was more pronounced in the cybrids harboring mtDNA deletions than in the control cybrid with wild‐type mtDNA. Subsequently, we evaluated the effect of coenzyme Q 10 on the UV‐triggered apoptosis. The results showed that after pretreatment of the cybrids with 100 μM coenzyme Q 10 the UV‐induced cell damage (i.e., ROS production and activation of caspase 3) was significantly reduced. Taken together, these findings suggest that large‐scale deletions of mtDNA increased the susceptibility of human cells to the UV‐triggered apoptosis and that coenzyme Q 10 mitigated the damage; hence, it might potentially serve as a therapeutic agent to treat mitochondrial diseases resulting from mtDNA deletions.