Periodic Reporting for period 4 - MITOsmORFs (Identification and analysis of novel mitochondrial proteins encoded by small open reading frames)
Berichtszeitraum: 2020-03-01 bis 2021-08-31
We determined the mitochondrial protein composition for model organism baker’s yeast and for human mitochondria. Mitochondria contain roughly 1000 proteins and we were able to identify more than 100 novel high-confidence mitochondrial proteins. Many of these were confirmed by single proteins studies involving e.g. fluorescence microscopy or import into isolated mitochondria. In addition, we determined mitochondrial protein copy numbers, half-lives, submitochondrial protein localizations, membrane protein topologies and mitochondrial proteins with multiple cellular localization. To analyze the functional role of novel mitochondrial proteins we identified their interacting proteins and we were able to identify many novel interactors of complexes required for cellular respiration.
By additional single protein studies we were e.g. able to identify proteins required for cellular respiration. We determined general relevance of the ‘conservative sorting’ pathway for the biogenesis of mitochondrial proteins combining the eukaryotic mitochondrial protein import system into mitochondria with the bacterial inherited protein export pathway. In addition, we determined the basic cell biology mechanism for the transport of hydrophobic membrane proteins through an aqueous mitochondrial subcompartment and for the assembly of membrane protein pores in the mitochondrial outer membrane. Moreover a systematic mapping of functional categories of 460 mitochondrial disease-related proteins with their associated disease observations provides a rich framework for defining the role of mitochondria in the pathogenesis of human diseases.