{"id":4196,"date":"2022-03-24T16:52:40","date_gmt":"2022-03-24T15:52:40","guid":{"rendered":"https:\/\/www.mc-praha.cz\/mcp\/?p=4196"},"modified":"2022-03-24T16:54:29","modified_gmt":"2022-03-24T15:54:29","slug":"degradovane-ghost-mitochondrie-podporuji-maligni-nadorove-procesy","status":"publish","type":"post","link":"https:\/\/www.mc-praha.cz\/mcp\/degradovane-ghost-mitochondrie-podporuji-maligni-nadorove-procesy\/","title":{"rendered":"Degradovan\u00e9 (\u201eghost\u201c) mitochondrie podporuj\u00ed malign\u00ed n\u00e1dorov\u00e9 procesy"},"content":{"rendered":"<p><strong>Metastazov\u00e1n\u00ed n\u00e1dor\u016f spojen\u00e9 s\u00a0pozm\u011bn\u011bn\u00fdm fungov\u00e1n\u00edm mitochondri\u00ed je charakteristick\u00e9 pro r\u016fzn\u00e9 typy malignit. Kontrola metast\u00e1z\u00ed skrze kl\u00ed\u010dov\u00fd mitochondri\u00e1ln\u00ed protein Mic60, \u00a0jeho\u017e redukce vede k\u00a0mitochondri\u00e1ln\u00ed degradaci, by mohla p\u0159edstavovat potenci\u00e1ln\u00ed terapeutickou mo\u017enost u obt\u00ed\u017en\u011b l\u00e9\u010diteln\u00fdch malignit.<\/strong><\/p>\n<p>Protein Mic60 (mitofilin) je struktur\u00e1ln\u00ed protein z\u00e1sadn\u00ed pro stavbu a funkce mitochondri\u00ed. \u0158\u00edd\u00ed d\u00fdchac\u00ed komplexy a zaji\u0161\u0165uje biogenezi vn\u011bj\u0161\u00ed mitochondri\u00e1ln\u00ed membr\u00e1ny. Jeho zv\u00fd\u0161en\u00e1 exprese podporuje tvorbu\u00a0mitochondri\u00e1ln\u00edch krist, a t\u00edm i aktivitu (vy\u0161\u0161\u00ed produkci ATP) a kondici mitochondri\u00ed v\u010detn\u011b d\u00e9lky jejich \u017eivotnosti.<\/p>\n<p>Gosh et al. (2022) zkoumali zapojen\u00ed Mic60 do n\u00e1dorov\u00fdch proces\u016f. P\u0159i malignit\u00e1ch doch\u00e1z\u00ed v\u00a0mitochondri\u00edch k redukci proteinu Mic60, kter\u00e1 mitochondrie akutn\u011b po\u0161kozuje, doch\u00e1z\u00ed k bioenergetick\u00fdm deficit\u016fm, k bun\u011b\u010dn\u00e9mu str\u00e1d\u00e1n\u00ed a spou\u0161t\u00ed se oxidativn\u00ed stres.<\/p>\n<p>Mitochondrie degradovan\u00e9 v\u00a0d\u016fsledku heterogenn\u00ed a sn\u00ed\u017een\u00e9 exprese Mic60, ozna\u010dovan\u00e9 jako p\u0159\u00edzraky (\u201eghost mitochondria\u201c), nepodl\u00e9haj\u00ed bun\u011b\u010dn\u00e9 smrti, ale funguj\u00ed d\u00e1le v\u00a0pozm\u011bn\u011bn\u00e9m re\u017eimu. Produkuj\u00ed kysl\u00edkov\u00e9 radik\u00e1ly (ROS) a st\u00e1vaj\u00ed se kl\u00ed\u010dov\u00fdmi faktory umo\u017e\u0148uj\u00edc\u00edmi metastazov\u00e1n\u00ed t\u00edm, \u017ee z\u00e1sobuj\u00ed energi\u00ed invazivn\u00ed bu\u0148ky.<\/p>\n<p>Heterogenn\u00ed expresi Mic60, nejsp\u00ed\u0161e z\u00e1vislou na stresov\u00fdch environment\u00e1ln\u00edch situac\u00edch, r\u016fstu n\u00e1dor\u016f, defektivn\u00edch oxidativn\u00edch funkc\u00edch, je t\u0159eba d\u00e1le zkoumat a objasnit.<\/p>\n<p>Kompenza\u010dn\u00ed aktivace program\u016f genov\u00e9 exprese i signalizace kin\u00e1z GCN2\/Akt umo\u017e\u0148uje n\u00e1dor\u016fm s n\u00edzk\u00fdm obsahem Mic60 p\u0159e\u017e\u00edvat. V\u011bdci p\u0159edpokl\u00e1daj\u00ed, \u017ee farmakologick\u00e1 l\u00e9\u010dba nebo genov\u00e1 terapie c\u00edlen\u00e1 na tyto dr\u00e1hy by mohly selektivn\u011b inhibovat proliferaci n\u00e1dorov\u00fdch bun\u011bk s n\u00edzk\u00fdm obsahem Mic60 a v\u00a0ur\u010dit\u00fdch p\u0159\u00edpadech l\u00e9\u010debn\u011b zafungovat.<\/p>\n<p>Ukazuje se, \u017ee mitochondrie, organely kl\u00ed\u010dov\u00e9 p\u0159edev\u0161\u00edm pro n\u00e1\u0161 energetick\u00fd metabolismus, mohou hr\u00e1t d\u016fle\u017eitou roli i v boji s\u00a0rakovinou. Perspektivn\u00edm terapeutick\u00fdm c\u00edlem zejm\u00e9na u obt\u00ed\u017en\u011b l\u00e9\u010diteln\u00fdch a k metastazov\u00e1n\u00ed n\u00e1chyln\u00fdch malignit by se mohlo st\u00e1t mitochondri\u00e1ln\u00ed p\u0159eprogramov\u00e1n\u00ed.<\/p>\n<p>V\u00a0Medic\u00ednsk\u00e9m centru Praha V\u00e1m m\u016f\u017eeme nab\u00eddnout otestov\u00e1n\u00ed mitochondri\u00ed na pr\u016ftokov\u00e9m cytometru (stanoven\u00ed procentu\u00e1ln\u00edho po\u010dtu mitochondri\u00ed nach\u00e1zej\u00edc\u00edch se v\u00a0apopt\u00f3ze), nebo ur\u010den\u00ed Va\u0161\u00ed mitochondri\u00e1ln\u00ed haploskupiny (zji\u0161t\u011bn\u00ed genetick\u00fdch ko\u0159en\u016f z\u00a0mat\u010diny strany).<\/p>\n<p>Ing. V\u00edt Smejkal<\/p>\n<p>24.3.2022<\/p>\n<p>Zdroj:<\/p>\n<p>Ghosh J.C., Perego M., Agarwal E., Bertolini I., Wang Y., Goldman A.R., Tang H.-Y., Kossenkov A.V., Libby C.J., Languino L.R., Plow E.F., Morotti A., Ottobrini L., Locatelli M., Speicher D.W., Caino M.C., Cassel J., Salvino J.M., Robert M.E., Vaira V., Altieri D.C. (2022): Ghost mitochondria drive metastasis through adaptive GCN2\/Akt therapeutic vulnerability. Proceedings of the National Academy of Sciences of the United States of America, 119, e2115624119. <a href=\"https:\/\/doi.org\/10.1073\/pnas.2115624119?fbclid=IwAR3Yv3-LFmGP5AHsed53XJchonZlWmePph2cdNK-OOCOtKWon-PFCFPxKD4\">https:\/\/doi.org\/10.1073\/pnas.2115624119<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Metastazov\u00e1n\u00ed n\u00e1dor\u016f spojen\u00e9 s\u00a0pozm\u011bn\u011bn\u00fdm fungov\u00e1n\u00edm mitochondri\u00ed je charakteristick\u00e9 pro r\u016fzn\u00e9 typy malignit. Kontrola metast\u00e1z\u00ed skrze [&hellip;]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"image","meta":{"_uag_custom_page_level_css":""},"categories":[1],"tags":[],"uagb_featured_image_src":{"full":false,"thumbnail":false,"medium":false,"medium_large":false,"large":false,"1536x1536":false,"2048x2048":false,"boldthemes_grid":false,"boldthemes_grid_11":false,"boldthemes_grid_22":false,"boldthemes_grid_21":false,"boldthemes_grid_12":false,"boldthemes_latest_posts":false,"boldthemes_grid_gallery":false},"uagb_author_info":{"display_name":"Jbednar","author_link":"https:\/\/www.mc-praha.cz\/mcp\/author\/jbednar\/"},"uagb_comment_info":0,"uagb_excerpt":"Metastazov\u00e1n\u00ed n\u00e1dor\u016f spojen\u00e9 s\u00a0pozm\u011bn\u011bn\u00fdm fungov\u00e1n\u00edm mitochondri\u00ed je charakteristick\u00e9 pro r\u016fzn\u00e9 typy malignit. Kontrola metast\u00e1z\u00ed skrze [&hellip;]","post_mailing_queue_ids":[],"_links":{"self":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts\/4196"}],"collection":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/comments?post=4196"}],"version-history":[{"count":1,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts\/4196\/revisions"}],"predecessor-version":[{"id":4198,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/posts\/4196\/revisions\/4198"}],"wp:attachment":[{"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/media?parent=4196"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/categories?post=4196"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.mc-praha.cz\/mcp\/wp-json\/wp\/v2\/tags?post=4196"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}