Mitochondrial gene eXpression

Introduction

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.

Current Understanding

To this end, we demonstrated that mitochondrial translation is prone to regulation, responding to the 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.

Project Proposal

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 basis for the challenging project proposed here, which aims to solve long-standing questions:

1. Dissecting Mitochondrial Transcript Interactomes
   First, we will dissect mitochondrial transcript interactomes and their spatial orchestration to understand basic principles of RNA abundance, organization in granules, and cross-communication.

2. Investigating Translation
   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, membrane insertion, and regulation.

3. In Vivo Transcript-Specific Silencing
   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.

Expected Outcomes

The combination of functional analyses carried out in organello and in vivo will provide unprecedented insights into the components and mechanisms of mitoGE and reveal how two genetically independent systems cooperate to build a functional metabolic pathway able to respond to energetic requirements and challenges.