The great majority of mitochondrial proteins is encoded on the nuclear genome. As a consequence, translation of these proteins in the cytosol is followed by their translocation into mitochondria. Compromised mitochondrial protein import has been linked to various pathologies. Up to this point, investigation of protein import into organelles remained challenging due to a lack of suitable tools. The team around Christian Münch developed a proteomics-based assay that allows examining mitochondrial protein uptake at the global scale in unperturbed cells.

As published now in Molecular Cell, they used this approach to determine protein uptake rates for more than 700 mitochondrial proteins and analyzed how uptake changes when mitochondrial fitness is acutely compromised. They showed that mitochondrial stress modulates protein uptake on two distinct levels: by attenuation of protein translation via the integrated stress response, and by disturbing protein import directly. To facilitate the application of this new proteomics tool, the team also provides a new software tool for data analysis (DynaTMT).