Import of mitochondrial proteins

Abstract

Publisher Summary This chapter describes the structural organization and function of the import systems that mediate protein targeting to mitochondria, and how genetic alterations of these systems contribute to the development of neurodegenerative disorders in humans. At the outer surface of the mitochondrial outer membrane, specific receptors are exposed that recognize and bind the precursors prior to their translocation. The transfer across the membranes is then mediated by the distinct import systems embedded in the outer and the inner membranes. Upon translocation of a precursor into the mitochondrial matrix, these machineries interact dynamically, thereby bringing the two membranes into close proximity. In eukaryotes, three distinct preprotein import systems have been described. Thus, an impaired quality control of mitochondrial inner-membrane proteins because of compromised chaperone or protease function leads to impaired oxidative phosphorylation (OXPHOS) function and neurodegeneration in humans. Defects in paraplegin may cause an accumulation of nonassembled subunits of respiratory-chain complexes or ATP-synthase, and may promote nucleation in neurodegeneration.