Role of transcription factors in mtDNA biogenesis mediated by thyroid hormones.

Exogenous thyroid hormones are regulators of cellular metabolism that involves, along with other cell structures, mitochondria. Mechanisms of the influence of thyroid hormones on the biogenesis of mtDNA are not fully understood due to their pleiotropic nature. Different ways of regulation of mitochondrial biogenesis by thyroid hormones are discussed in literature, but thyroid receptors, localized in both the nucleus and mitochondria, are the main elements of most pathways. Data on events occurring after receptor activation are rather contradictory. We investigated the degree of involvement of mitochondrial transcription factors in the biogenesis of mtDNA induced by triiodothyronine. The contribution of TFAM, TFB2M, and helicase Twinkle in thyroid-induced mtDNA biogenesis was assessed. The activation of TFAM and TFB2M expression is shown to be required for the induction of mtDNA biogenesis. The role of helicase Twinkle, the expression induction of which is also observed after triiodothyronine addition, remains unclear. The analysis of factors that activate TFAM and TFB2M expression showed that NRF-1 is the determinative regulator: deficiency of this factor leads to complete collapse of mtDNA biogenesis. However, lack of transcriptional coactivator PGC-1α did not lead to significant reduction in thyroid-induced biogenesis, whereas literature data point to its key role in the biogenesis of mitochondria. Thus, in this study the role of key transcription factors in mtDNA biogenesis induced by triiodothyronine was demonstrated for the first time in a model system.

[Release of mtDNA from mitochondria and activation of its replication in tissues of irradiated mice].

A nessessary condition for normal functioning of mitochondria is the maintenance of certain numbers of intact mtDNA molecules. In the present study, we investigasted changes in the number of mtDNA copies in brain and spleen cells of mice subjected to irradiation. For the first time, we observed the irradiation-induced output of mtDNA fragments into brain and spleen cell cytosol. In the cytosol of these cells, examined in mice 5 h after 5 Gy irradiation, 1841 h.p. mtDNA fragments were detected able to persist for at 3 weeks. In addition, larger fragments of mtDNA (10,090 b.p.) were detected in the cytosol of brain cells of irradiated mice. The occurrence of mtDNA fragments in the cytosol of brain cells is accompanied with an increase in the number of mtDNA copies in the mitochondrial matrix. The induction of mtDNA replication in brain cells of irradiated animals may be considered as a compensatory reaction in response to mtDNA damage. A sharp decrease in the amount of mtDNA copies in the mitochondrial matrix of spleen cells on the first day after irradiation may be considered as apoptosis development. However, the compensatory reaction in brain cells was also noticed but in later terms.

Mitochondrial permeability transition triggers the release of mtDNA fragments.

Fragments of mitochondrial DNA are released from mitochondria upon opening of the mitochondrial permeability transition pore. Cyclosporin A, an inhibitor of pore opening, completely prevented the release of mitochondrial fragments. Induction of mitochondrial permeability transition and subsequent release of the fragments of mitochondrial DNA could be one cause of genomic instability in the cell.

[New subspecies of Prosimulium macropyga korshunovi Patrusheva subsp. n. (Diptera, Simuliidae) from the Polar Urals]. / Novyi podvid Prosimulium macropyga korshunovi Patrusheva subsp. n. (Diptera, Simuliidae) s Poliarnogo Urala

A new subspecies, Prosimulium macropyga korshunovi Patr. subsp. n., from the Polar Urals differs from other forms of P. macropyga (Lundstr.) and allied species in having two dark longitudinal stripes on the dorsum and by the structure of genitalia in adult insects, by the number of setae in the great flabellum, by the structure of submentum and shape of the ventral incision in larvae and by the branching pattern of respiratory threads in pupa.