SUMO-dependent control of mitochondrial protein biogenesis

• Applicant: Dr. Fabian den Brave
• Subject Area: Biochemistry
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 529716110

Mitochondria are essential organelles performing a multitude of cellular functions including ATP production through oxidative phosphorylation as well as the biosynthesis of amino acids, lipids, heme and iron-sulfur clusters. The vast majority of mitochondrial proteins are nuclear encoded and synthesized on cytosolic ribosomes. Defects in targeting or import of mitochondrial precursor proteins result in impaired mitochondrial function and an accumulation of mitochondrial proteins outside mitochondria. Damaged or prematurely folded proteins might clog the import channel, thereby impairing mitochondrial protein import and biogenesis. Consequently, it is crucial to understand how cells ensure fidelity of protein transport into mitochondria. Recent findings have demonstrated an important role of the cytosolic ubiquitin-proteasome system in mitochondrial import quality control. We observed that the ubiquitin-like modifier SUMO is attached to mitochondrial proteins in particular upon impaired protein import into mitochondria. However, the function of this post-translational modification has remained enigmatic. Here we investigate the role of the SUMO pathway in the biogenesis of mitochondrial proteins.

• DFG Programme: Research Grants