Description du projet
Connaissances mécanistes de l’expression des gènes mitochondriaux
En plus de l’ADN nucléaire, les cellules eucaryotes contiennent de l’ADN mitochondrial, qui code les sous-unités des enzymes de la chaîne de transport des électrons. Bien que cela soit clairement révélateur de l’importance de l’expression des gènes mitochondriaux pour le métabolisme cellulaire, les connaissances mécanistes de son exécution et de sa régulation demeurent lacunaires. Ce que l’on sait, c’est que la traduction des gènes mitochondriaux est régulée par l’action de facteurs codés par le noyau. Financé par le Conseil européen de la recherche, le projet MiXpress propose d’examiner les différentes étapes du processus d’expression des gènes mitochondriaux. Il mettra l’accent sur la coopération avec les composants codés par le noyau afin de comprendre la manière dont les cellules répondent aux besoins énergétiques.
Objectif
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.
Champ scientifique
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-AG - HORIZON Action Grant Budget-BasedInstitution d’accueil
37075 Goettingen
Allemagne