Protein Quality Control



Head: Dr. Christian Münch

Mitochondria are essential for most cellular processes and a cell’s very own survival. To remain active and functional, mitochondria need to control the synthesis and folding of their proteins. However, many cellular perturbations, including major diseases like neurodegenerative diseases and cancer, can harm mitochondria’s protein folding homeostasis, with potentially fatal consequences for cells.


Figure: UPRmt halts mitochondrial translation.
From Münch and Harper, Nature 2016.

Research in the Münch laboratory focuses on the mitochondrial protein quality control responses in mammalian cells upon mitochondrial protein misfolding, particularly the mitochondrial unfolded protein response (UPRmt). During protein folding stress in mitochondria, UPRmt elicits a transcriptional response to induce genes such as chaperonins to increase the mitochondrial folding capacity. Additionally, as we recently showed, UPRmt also contains a translational response that reduces the folding load of proteins inside mitochondria by reversibly halting mitochondrial translation (Figure). Using cutting-edge cell biological and biochemical techniques such as quantitative mass spectrometry, CRISPR/Cas9 editing, and next-generation sequencing, we aim to further understand and define the processes involved in the UPRmt and other mitochondrial stress responses upon protein misfolding, and to gain insight into the pathways that protect from mitochondrial and cellular damage.