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001-es BibID:	BIBFORM091671
035-os BibID:	(cikkazonosító)105326 (WOS)000615153300011 (Scopus)85098672142
Első szerző:	Bachmann, Magdalena
Cím:	Synthesis and cellular effects of a mitochondria-targeted inhibitor of the two-pore potassium channel TASK-3 / Magdalena Bachmann, Andrea Rossa, Giuseppe Antoniazzi, Lucia Biasutto, Andrea Carrer, Monica Campagnaro, Luigi Leanza, Monika Gonczi, László Csernoch, Cristina Paradisi, Andrea Mattarei, Mario Zoratti, Ildiko Szabo
Dátum:	2021
ISSN:	1043-6618
Megjegyzések:	The two-pore potassium channel TASK-3 has been shown to localize to both the plasma membrane and the mitochondrial inner membrane. TASK-3 is highly expressed in melanoma and breast cancer cells and has been proposed to promote tumor formation. Here we investigated whether pharmacological modulation of TASK-3, and specifically of mitochondrial TASK-3 (mitoTASK-3), had any effect on cancer cell survival and mitochondrial physiology. A novel, mitochondriotropic version of the specific TASK-3 inhibitor IN-THPP has been synthesized by addition of a positively charged triphenylphosphonium moiety. While IN-THPP was unable to induce apoptosis, mitoIN-THPP decreased survival of breast cancer cells and efficiently killed melanoma lines, which we show to express mitoTASK-3. Cell death was accompanied by mitochondrial membrane depolarization and fragmentation of the mitochondrial network, suggesting a role of the channel in the maintenance of the correct function of this organelle. In accordance, cells treated with mitoIN-THPP became rapidly depleted of mitochondrial ATP which resulted in activation of the AMP-dependent kinase AMPK. Importantly, cell survival was not affected in mouse embryonic fibroblasts and the effect of mitoIN-THPP was less pronounced in human melanoma cells stably knocked down for TASK-3 expression, indicating a certain degree of selectivity of the drug both for pathological cells and for the channel. In addition, mitoIN-THPP inhibited cancer cell migration to a higher extent than IN-THPP in two melanoma cell lines. In summary, our results point to the importance of mitoTASK-3 for melanoma cell survival and migration.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk Mitochondria TASK-3 potassium channel Pharmacological targeting Melanoma
Megjelenés:	Pharmacological Research. - 164 (2021), p. 105326. -
További szerzők:	Rossa, Andrea Antoniazzi, Giuseppe Biasutto, Lucia Carrer, Andrea Campagnaro, Monica Leanza, Luigi Gönczi Mónika (1974-) (élettanász) Csernoch László (1961-) (élettanász) Paradisi, Cristina Mattarei, Andrea Zoratti, Mario Szabó Ildikó
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