"2014-03-31+02:00"^^ . "ATP synthase is the key enzyme of mitochondrial energy provision, responsible for production of most cellular ATP. Enzyme biogenesis results from expression of both nuclear and mtDNA genes encoding 16 different types of enzyme subunits that are assembled into a functional ATP synthase in a stepwise process that depends on several helper proteins. Recently we have discovered a new type of ATP synthase ancillary factor, the TMEM70, that is the first factor specific for higher eukaryotes. Its \u00A0mutation leads to enzyme deficiency and results in fatal mitochondrial disease (Nature Genetics 2008, 40:1228). The aim of the project is to characterize the biological role of this factor at structural and functional levels and further elucidate the mechanism of mammalian ATP synthase biogenesis. Project will be based on investigation of unique cellular models and generation of \u00A0TMEM70 conditional, tissue specific (Cre/LoxP) knockout mice. Proposed studies will have direct impact on better understanding of\u00A0 molecular pathogenesis of human mitochondrial diseases."@en . . . . "2011-01-01+01:00"^^ . . "6"^^ . . "6"^^ . . . "Mechanism of ATP synthase biogenesis and the role of TMEM70 protein"@en . "2015-12-31+01:00"^^ . "0"^^ . "Mechanismus biogeneze ATP synt\u00E1zy a \u00FAloha faktoru TMEM70" . "2015-04-23+02:00"^^ . "mitochondria inborn errors ATP synthase biogenesis assembly factor TMEM70 knockdown and knockout models"@en . . . "1"^^ . . "0"^^ . "http://www.isvav.cz/projectDetail.do?rowId=GAP303/11/0970"^^ . . "GAP303/11/0970" . . . "ATP synt\u00E1za je kl\u00ED\u010Dov\u00FDm enzymem mitochondri\u00E1ln\u00EDho energetick\u00E9ho metabolismu a je odpov\u011Bdn\u00E1 za tvorbu v\u011Bt\u0161iny bun\u011B\u010Dn\u00E9ho ATP. Biogeneze ATP synt\u00E1zy je v\u00FDsledkem exprese jadern\u00FDch a mitochondri\u00E1ln\u00EDch (mtDNA) gen\u016F a postupn\u00E9ho sestaven\u00ED enzymu z \u00A016ti typ\u016F podjednotek, \u00A0za \u00FA\u010Dasti n\u011Bkolika pomocn\u00FDch protein\u016F. Na\u0161e posledn\u00ED studie vedly k objevu nov\u00E9ho typu pomocn\u00E9ho faktoru, TMEM70, kter\u00FD je\u00A0 prvn\u00EDm faktorem specifick\u00FDm pro vy\u0161\u0161\u00ED eukaryonty. Jeho mutace m\u00E1 za n\u00E1sledek defekt biosynt\u00E9zy ATP synt\u00E1zy a\u00A0 vede k fat\u00E1ln\u00ED mitochondri\u00E1ln\u00ED chorob\u011B (Nature Genetics 2008, 40:1228). C\u00EDlem projektu je charakterizovat biologickou roli tohoto faktoru na strukturn\u00ED a funk\u010Dn\u00ED \u00FArovni a d\u00E1le \u00A0objasnit mechanismus biogeneze sav\u010D\u00ED ATP synt\u00E1zy. V projektu budou vyu\u017Eity unik\u00E1tn\u00ED bun\u011B\u010Dn\u00E9 modely a my\u0161\u00ED model TMEM70 kondiciovan\u00E9ho, tk\u00E1\u0148ov\u011B specifick\u00E9ho (Cre/LoxP) knockoutu, kter\u00FD bude p\u0159ipraven. Navrhovan\u00E9 studie p\u0159isp\u011Bj\u00ED k objasn\u011Bn\u00ED molekul\u00E1rn\u00EDch mechanism\u016F patogeneze lidsk\u00FDch mitochondri\u00E1ln\u00EDch chorob." . . . . . . .