Translocation of Proteins into Mitochondria

Abstract

About 10% to 15% of the nuclear genes of eukaryotic organisms encode mitochondrial proteins. These proteins are synthesized in the cytosol and recognized by receptors on the surface of mitochondria. Translocases in the outer and inner membrane of mitochondria mediate the import and intramitochondrial sorting of these proteins; ATP and the membrane potential are used as energy sources. Chaperones and auxiliary factors assist in the folding and assembly of mitochondrial proteins into their native, three-dimensional structures. This review summarizes the present knowledge on the import and sorting of mitochondrial precursor proteins, with a special emphasis on unresolved questions and topics of current research.

The presequence pathway is involved in protein sorting to the mitochondrial outer membrane

“…Tom20 and Tom22 play a major role in the import of presequence-carrying proteins into mitochondria, whereas the third receptor Tom70 is important for importing non-cleavable carrier proteins [2,3]. To study whether Tom20 and Tom22 were involved in the import of Om45, we incubated the 35 S-labelled precursor of Om45 with isolated mitochondria.…”

“…Tom5 is closely associated with Tom40 and involved in the import of preproteins, whereas Tom6 and Tom7 play a role in the assembly and dynamics of TOM [2][3][4][5]. Mitochondria lacking Tom5 were impaired in import and assembly of Om45, whereas tom6D and tom7D mitochondria imported Om45 like wild-type mitochondria (Fig 2A).…”

The direct route: a simplified pathway for protein import into the mitochondrion of trypanosomes

“…Membrane proteins are transferred instead to the TIM22 complex in the inner membrane or the sorting and assembly machinery (SAM complex) in the outer membrane for membrane insertion and assembly. A set of 'tiny TIMs' in the intermembrane space can drive this transfer of substrate protein from the TOM complex [26,27,32].…”

Structural basis for unfolding pathway‐dependent stability of proteins: Vectorial unfolding versus global unfolding

“…9,10 Mitochondrial protein import is mediated by the membrane protein complexes called translocators in the outer and inner mitochondrial membranes. [10][11][12] Protein translocators contain receptor(s) that recognize the targeting and/or sorting signals encoded in the presequence or mature domain of substrate proteins and a protein-conducting channel through which mitochondrial proteins traverse the hydrophobic barrier of the mitochondrial membranes. When incubated with isolated mitochondria, the I27 domain fused to a mitochondrial targeting signal can be unfolded to move through the narrow pores of the translocator complexes in the outer and inner mitochondrial membranes.…”