Protein translocation into mammalian mitochondria and its role in the development of human mitochondrial disorders
Hofmann S, Bauer MF
Topics in Current Genetics (2004)
Category: mitochondria-biogenesis, mitochondrial diseases ¤ Added: Jun 02, 2004 ¤ Rating: ◊◊
Major aspects of mitochondrial biogenesis are the transfer of nuclear encoded proteins into the organelle by a sophisticated protein translocation machinery and their assembly into functional complexes. Most of the yeast components involved in the import and assembly of mitochondrial preproteins have counterparts in mammalian mitochondria, suggesting an evolutionary conservation of the import machinery and pathways in the eukaryotic kingdom. Most recently, the structural and functional similarities between the yeast and human import pathways have allowed the elucidation of a new mitochondrial disease on the molecular level. This rare X-linked progressive neurodegenerative disorder, named Mohr-Tranebjaerg syndrome (MTS), is caused by mutations in DDP1. The homologous yeast protein, Tim8, is involved in the import of hydrophobic proteins into the mitochondrial inner membrane. In this review, we summarize the current knowledge on components and mechanisms of protein import into mammalian mitochondria with a special focus on the role of DDP1 and its yeast counterpart Tim8, thereby, providing a link between the molecular basis of mitochondrial biogenesis and mitochondrial medicine.