The role of Por1 and its partner protein Om14 in mitochondrial protein import

• Applicant: Professor Dr. Thomas Becker
• Subject Area: Biochemistry
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 528247081

Mitochondrial biogenesis and functions depend on the import of more than 1000 proteins that are produced as precursors on cytosolic ribosomes. The translocase of the outer membrane (TOM complex) forms the entry site for almost all mitochondrial proteins. Subsequently, dedicated protein translocases sort the precursor proteins into the outer and inner membranes, the intermembrane space and matrix. While transport steps are understood to some detail only little is known how protein transport is modulated during metabolic adaptation. Mitochondrial protein biogenesis has to be adjusted to ensure the dramatic changes of the protein content during shift from fermentative to respiratory growth conditions, including strongly increased levels of proteins involved in respiratory metabolism. Recently, we have uncovered in baker`s yeast that the major outer membrane channel for metabolites and ions Por1 (also termed VDAC for voltage dependent anion channel) acts as coupling factor to promote import of carrier proteins. We furthermore found that Por1 interacts the protein translocases of the outer membrane, including the TOM complex, the sorting and assembly machinery (SAM complex) that inserts -barrel proteins and the mitochondria import (MIM complex) machinery that inserts proteins with -helical membrane anchor. Similarly, Om14 that forms a complex with Por1 interacts with TOM and MIM complexes, but not with the SAM complex. In this project, we will analyze the role of Por1 and Om14 in mitochondrial protein import and study their impact on outer membrane protein biogenesis. Our studies will reveal whether molecular coupling of mitochondrial protein translocases to Por1 and Om14 represents a new principle to modulate protein import capacity in response to metabolic adaptation during nutrient change. We will define the role of Por1 and Om14 to maintain mitochondrial protein content during metabolic adaptation. Since Om14 was reported to act as docking site for cytosolic ribosomes, we will investigate whether Om14 promotes co-translational protein import. Our studies will address the fundamental cell biological question how the mitochondrial protein biogenesis is adjusted in response to nutrient changes.

• DFG Programme: Research Grants