Understanding the molecular mechanism of protein translocation across the mitochondrial inner membrane: Still a long way to go

Abstract

In order to reach the final place of their function, approximately half of the proteins in any eukaryotic cell have to be transported across or into one of the membranes in the cell. In this article, we present an overview of our current knowledge concerning the structural properties of the TIM23 complex and their relationship with the molecular mechanism of protein transport across the mitochondrial inner membrane. This article is part of a Special Issue entitled Protein translocation across or insertion into membranes.

Phosphatidylcholine Affects Inner Membrane Protein Translocases of Mitochondria

“…The TIM23 complex mediates protein transport into the matrix and lateral release into the inner membrane. TIM23 subunits dynamically interact with the PAM module for transport into the matrix (3)(4)(5)(6)(7)(8)(9). Furthermore, the TIM23 complex interacts with the TOM complex during preprotein transfer.…”

“…For transport into the mitochondrial matrix, the TIM23 complex dynamically associates with the presequence translocase-associated motor (PAM). The ATP consuming activity of the mitochondrial Hsp70 within the PAM module completes preprotein transport into the matrix (3)(4)(5)(6)(7)(8)(9). Finally, the presequence is removed by the mitochondrial processing peptidase.…”

“…Two inner membrane-bound protein complexes mediate protein import. The presequence translocase (also termed TIM23 complex) transports precursor proteins with a cleavable presequence into the inner membrane and the matrix, whereas the carrier translocase (also termed TIM22 complex) inserts proteins with multiple transmembrane segments into the inner membrane (3)(4)(5)(6)(7)(8)(9). The membrane potential across the inner membrane provides the driving force for both protein import pathways and is generated by the activity of the respiratory chain.…”

“…More than 99% of the mitochondrial proteins are synthesized as precursors on cytosolic ribosomes. Mitochondria contain a sophisticated system of protein translocases to import precursor proteins (3)(4)(5)(6)(7)(8)(9). The translocase of the outer membrane (TOM 3 complex) forms the general entry gate for most precursor proteins.…”

Architecture of the TIM23 Inner Mitochondrial Translocon and Interactions with the Matrix Import Motor

“…Most proteins destined for the matrix have an amino-terminal targeting sequence (presequence) whose translocation across the inner membrane is driven by the membrane potential. For complete translocation, the TIM23 complex cooperates with a heat shock protein 70 (Hsp70)-based, PAM (presequence translocase-associated motor) complex, which resides on the matrix side of the inner membrane (10,11).…”