Mitochondria play an important role in metabolism and regulatory processes in the cell. Thus, the formation of mitochondria is essential for cellular function in the entire eukaryotic kingdom, from unicellular organisms to mammals. Mitochondria comprise 1000-1500 cellular proteins, which are synthesized outside of the mitochondria in the cytosol.
The biogenesis of mitochondria relies on the efficient import, sorting, and maturation of proteins governed by conserved protein translocases and other complex machineries. We identified a novel mitochondrial intermembrane space assembly (MIA) pathway that utilizes the transfer of disulfide bonds and is dedicated to the import and biogenesis of intermembrane space proteins that lack a classical mitochondrial leader sequence.