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Федеральное государственное бюджетное учреждение науки
"Институт токсикологии Федерального медико-биологического агентства"
(ФГБУН ИТ ФМБА России)

Институт теоретической и экспериментальной биофизики Российской академии наук.

ООО "ИЦ КОМКОН".




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199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314

Российская поисковая система
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«
Vol. 13, Art. 46 (pp. 566-582)    |    2012       
»

Nuclear regulation of mitochondrial dna biogenesis in mouse liver following X-ray irradiation
Gubina N.E.*, Evdokimovsky E.V, Ushakova T.E.

Institute of Theoretical and Experimental Biophysics RAS



Brief summary

It is widely believed now that mitochondria are the remnants of symbiotic organisms which have entered the eukaryotic cell about two billion years ago. In the course of the evolution most of mitochondrial genes, including all the genes regulating mitochondrial transcription and replication machinery, has been transferred into nucleus. By this moment great advances have been achieved in understanding the role of individual nuclear genes in the regulation of mitochondrial biogenesis. However, it is still unknown, how the whole system responds to the oxidative stress, in particular, X-ray irradiation. We have focused our investigation on a regulatory cascade chain composed of two factors, recognizing external signals (nuclear coactivator PGC-1α, nuclear corepressor RIP140), nuclear respiratory factor NRF2 and three components of mitochondrial transcription and replication machinery (Polrmt, Tfam, Tfb2m). Using quantitative real-time PCR we have estimated transcription levels of all these factors in mouse liver at different time points following X-ray irradiation at the dose of 10 Gy. Reduction in transcription levels of Polrmt and Tfb2m correlates with inhibition of mtDNA transcription, and dynamics of Tfam, NRF2, PGC-1α and RIP140 transcription levels is connected to initiation of mtDNA replication. The divergence in the dynamics of expression of Polrmt, Tfb2m and Tfam, NRF2, PGC-1α suggests that in the mouse liver under oxidative stress mtDNA transcription and replication may be regulated differentially. Probably, in radioresistant cells nuclear regulation of mitochondrial genome functions under irradiation represents an element of defense mechanism preventing synthesis of defect proteins and purifying the mtDNA pool from mutant copies.


Key words

мтДНК, мтРНК, регуляция экспрессии генов, рентгеновское облучение, печень, мыши





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