Descripción del proyecto
Mecanismos de expresión génica mitocondrial
Además del ADN nuclear, las células eucariotas contienen ADN mitocondrial, que codifica las subunidades de las enzimas de la cadena transportadora de electrones. Aunque ello indica claramente la importancia de la expresión génica mitocondrial en el metabolismo celular, se dispone de pocos conocimientos mecanicistas sobre cómo se consigue y regula. Se sabe que la traslación genética mitocondrial se regula mediante la acción de factores codificados por el núcleo. El equipo del proyecto MiXpress, financiado por el Consejo Europeo de Investigación, se propone investigar las distintas etapas del proceso de expresión génica mitocondrial. Se pondrá énfasis en la cooperación con componentes codificados en el núcleo para comprender cómo responden las células a las necesidades energéticas.
Objetivo
Mitochondrial gene expression is essential for cellular metabolism and energy supply since 13 core subunits of the OXPHOS system are encoded on the mitochondrial genome. Despite its importance for cellular function, mitochondrial gene expression (mitoGE) and its regulation are not understood at a mechanistic level. To this end, we demonstrated that mitochondrial translation is prone to regulation, responding to influx of nuclear-encoded proteins . However, the mechanisms that regulate gene expression in mitochondria remain unknown. A lack of suitable experimental approaches to modulate mitoGE hampers progress in our understanding. Here I propose a project that takes the next big step towards understanding the mechanisms of mitochondrial gene expression. Our recent work on an in organello system to target mitoGE in a transcript-specific manner provides the bases for the challenging project proposed here, which aims to solve long-standing questions: First, we will dissect mitochondrial transcript interactomes and their spatial orchestration to understand basic principles of RNA abundance, organization in granules, and cross communication. Second, we are now able to investigate translation in the context of the inner membrane with transcript-specific resolution and thereby identify liaising factors involved in ribosome recruitment and membrane insertion and regulation. Third, we will extend our strategy towards an in vivo transcript-specific silencing approach to define retrograde signaling pathways that integrate mitoGE into cellular contexts. The combination of functional analyses carried out in organello and in vivo will provide unprecedented insights into components and mechanism of mitoGE and reveal how two genetically independent systems cooperate to build a functional metabolic pathway able to respond to energetic requirements and challenges.
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-AG - HORIZON Action Grant Budget-BasedInstitución de acogida
37075 Goettingen
Alemania