{"id":97385,"date":"2018-03-11T10:17:55","date_gmt":"2018-03-11T10:17:55","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/identificacion-y-propiedades-funcionales-de-variantes-de-splicing-de-mitofusina\/"},"modified":"2018-03-11T10:17:55","modified_gmt":"2018-03-11T10:17:55","slug":"identificacion-y-propiedades-funcionales-de-variantes-de-splicing-de-mitofusina","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/acidos-nucleicos\/identificacion-y-propiedades-funcionales-de-variantes-de-splicing-de-mitofusina\/","title":{"rendered":"Identificaci\u00f3n y propiedades funcionales de variantes de \u00absplicing\u00bb de mitofusina"},"content":{"rendered":"<h2>Tesis doctoral de <strong> D\u00e9borah Paola Na\u00f3n Elbirt <\/strong><\/h2>\n<p>Mutaciones en el gen de mfn2 causan la neuropat\u00eda charcot-marie-tooth type 2a (zuchner et al., Nature genetics 2004). Mitofusina 2  se encuentra expresada en niveles elevados en tejidos como m\u00fasculo, coraz\u00f3n y cerebro, los mecanismos por los cuales las mutaciones de mfn2 causan esta patolog\u00eda restringida al sistema nervioso perif\u00e9rico, se desconocen. Hasta ahora, solo se considera que el gene de mfn2 produce solo una prote\u00edna que participa en la fusi\u00f3n mitocondrial. En la presente tesis se demuestra la existencia de productos de splicing alternativo de mfn2, los cuales generan al menos 3 prote\u00ednas adicionales. Estas variantes muestran un patr\u00f3n de localizaci\u00f3n subcelular diferente a mfn2, y que presentan  funciones relevantes en morfolog\u00eda organular, ciclo celular, metabolismo del calcio en ret\u00edculo endoplasm\u00e1tico.   en la presente tesis demostramos que algunas de las variantes de mitofusina 2 son exclusivas de ret\u00edculo endoplasm\u00e1tico y que no poseen efectos en el metabolismo ni en la morfolog\u00eda mitocondrial a diferencia de mfn2 full length. Estas variantes  exclusivas de ret\u00edculo endoplasm\u00e1tico se detentan en distintos tejidos y c\u00e9lulas humana. Adem\u00e1s la re-expresi\u00f3n de mfn2 en c\u00e9lulas knock out  para mfn2, rescata la morfolog\u00eda de ret\u00edculo endoplasm\u00e1tico alterada en \u00e9ste modelo celular, y a su vez, normaliza los niveles de  calcio del org\u00e1nulo. Las variantes de mitofusina 2 presentan un potente efecto antiproliferativo que est\u00e1 mediados en parte por el contenido calcio del ret\u00edculo endoplasm\u00e1tico y el inhibidor de ciclo celular p27 kip.  En conjunto, el hallazgo de variantes de mfn2 exclusivamente de ret\u00edculo endoplasm\u00e1tico , revela la existencia  de funciones de mfn2 que son completamente extramitocondriales. Este hecho puede tener consecuencias relevantes para comprender las bases patofisiol\u00f3gicas de la enfermedad charcot-marie-tooth type 2a causada por mutaciones en el gen de mfn2.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Identificaci\u00f3n y propiedades funcionales de variantes de \u00absplicing\u00bb de mitofusina<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Identificaci\u00f3n y propiedades funcionales de variantes de \u00absplicing\u00bb de mitofusina <\/li>\n<li><strong>Autor:<\/strong>\u00a0 D\u00e9borah Paola Na\u00f3n Elbirt <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Barcelona<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 23\/11\/2009<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Antonio Zorzano Olarte<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: francesc Palau mart\u00ednez <\/li>\n<li>Mar\u00eda  isabel Fabregat romero (vocal)<\/li>\n<li>  (vocal)<\/li>\n<li>  (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de D\u00e9borah Paola Na\u00f3n Elbirt Mutaciones en el gen de mfn2 causan la neuropat\u00eda charcot-marie-tooth type 2a (zuchner [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-gradient":""}},"footnotes":""},"categories":[114,951,212,36483],"tags":[20202,199582,54197,14581],"class_list":["post-97385","post","type-post","status-publish","format-standard","hentry","category-acidos-nucleicos","category-barcelona","category-biologia-humana","category-biologia-molecular","tag-antonio-zorzano-olarte","tag-deborah-paola-naon-elbirt","tag-francesc-palau-Martinez","tag-maria-isabel-fabregat-romero"],"_links":{"self":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/97385","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/comments?post=97385"}],"version-history":[{"count":0,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/posts\/97385\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/media?parent=97385"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/categories?post=97385"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.deberes.net\/tesis\/wp-json\/wp\/v2\/tags?post=97385"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}