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The p53‐Dependent Expression of Frataxin Controls 5‐Aminolevulinic Acid‐Induced Accumulation of Protoporphyrin IX and Photo‐Damage in Cancerous Cells
Author(s) -
Sawamoto Mari,
Imai Takafumi,
Umeda Mana,
Fukuda Koji,
Kataoka Takao,
Taketani Shigeru
Publication year - 2012
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2012.01215.x
Subject(s) - frataxin , ferrochelatase , gene silencing , heme , protoporphyrin ix , chemistry , microbiology and biotechnology , mitochondrion , protoporphyrin , hek 293 cells , biology , biochemistry , gene , aconitase , enzyme , porphyrin , photodynamic therapy , organic chemistry
Mitochondrial frataxin is involved in various functions such as iron homeostasis, iron–sulfur cluster biogenesis, the protection from oxidative stress and apoptosis and acts as a tumor suppressor protein. We now show that the expression of frataxin is stimulated in a p53‐dependent manner and prove that frataxin is a direct p53 target gene by showing that the p53‐responsive element in the promoter of the mouse frataxin gene is bound by p53. The bacterial expression of human frataxin stimulated maturation of human ferrochelatase, which catalyzes the insertion of iron into protoporphyrin at the last step of heme biosynthesis. Overexpression of frataxin in human cancer A431 and HeLa cells lowered 5‐aminolevulinic acid( ALA )‐induced accumulation of protoporphyrin and induced resistance to ALA ‐induced photo‐damage, whereas p53 silencing with si RNA in non tumor HEK 293T cells down‐regulated the expression of frataxin and increased the accumulation of protoporphyrin. Thus, the decrease of the expression of frataxin unregulated by p53 in tumor cells enhances ALA ‐induced photo‐damage, by down‐regulation of mitochondrial functions.