Deciphering the role of specialized mitoribosomes in proteotoxic stress and ageing
Main PI:Verena Kohler, Department of Molecular Biology
Co-PI:Andreas Kohler, Department of Medical Biochemistry and Biophysics
Abstract
Mitochondrial function relies on a finely tuned interplay between organelle-specific and cytosolic protein synthesis systems. While adaptive changes in cytosolic translation under stress are well-documented, the corresponding dynamics within mitochondrial translation machinery remain poorly understood, particularly in the context of ageing and proteotoxic environments. This project investigates how mitochondrial protein synthesis systems respond to cellular stress and ageing, aiming to uncover fundamental principles of organelle adaptation and intercompartmental communication. The findings are expected to inform broader strategies for maintaining proteostasis and cellular resilience in age-associated conditions.
Objectives
1. Establish cellular models to explore the adaption of mitochondrial protein synthesis during stress and ageing
2. Define triggers and molecular signatures of mitochondrial translation remodelling under stress and ageing.
3. Identify signalling pathways that synchronize mitochondrial translation with cytosolic protein synthesis.
About the PIs and their synergies
Verena Kohler brings expertise in genome‐wide ageing screens, with her main research focus on the interorganellar chaperone network and stress communication between organelles during ageing. Andreas Kohler investigates the molecular mechanisms of mitochondrial translation and the quality control of nascent, mitochondrially-encoded proteins. By uniting Verena’s large-scale, unbiased screening approach with Andreas’s high-resolution biochemical and proteomic analyses—two methodological strengths not previously combined in our lab—we’ll access a new layer of cellular communication and translational coordination. This conceptually and technically innovative strategy will uncover previously unaddressed mechanisms with important implications for ageing and age-related diseases.
