CIBSS Area A

Dissection of protective signalling networks upon mitochondrial dysfunction

Prof. Dr. Nora Vögtle (CIBSS-AI), Centre for Molecular Biology Heidelberg, University of Heidelberg

CIBSS Profile page

 

Cells can sense mitochondrial dysfunction and respond by initiation of a protective nuclear transcriptional program known as mitochondrial unfolded protein response (mtUPR). We have established a reversible mtUPR model in the yeast S. cerevisiae which allows us to investigate the temporal stages upon mitostress. We already identified two novel protective mechanisms: The translocation of the nuclear transcription factor Rox1 into mitochondria upon stress is required to maintain the mitochondrial genome (Poveda-Huertes et al., 2020) and the increase in the mitochondrial signature lipid cardiolipin stabilizes the mitochondrial protein import machineries to uphold influx of cytosolic precursors upon stress conditions (Poveda-Huertes et al., 2021). Now we aim to identify, characterize and manipulate the signalling networks that mediate mitochondrial and cellular protection. We will first focus on Rox1 that is dynamically changing its location between the nucleus and mitochondria depending on mitochondrial fitness. We want to identify i) the signal switch within Rox1 that decides about its final localization and ii) the upstream signalling cascade that triggers the signal switch.