The Protein Import System of Mitochondria

Gottfried Schatz

doi:10.1074/jbc.271.50.31763

Abstract

The Protein Import System of Mitochondria

Highlights

A protein destined to be imported into mitochondria is normally synthesized with a transient N-terminal extension that functions as a targeting signal
Proteins imported into other mitochondrial subcompartments usually have an additional signal downstream from the matrix targeting signal; in many instances, this “sorting signal” interrupts translocation across either the outer or the inner membrane, thereby rerouting the protein to the outer membrane, the intermembrane space, or the inner membrane
It is still not settled whether mitochondrial protein import in vivo is cotranslational [14, 15], but in intact cells under physiological conditions the mitochondrial surface is essentially devoid of bound cytosolic ribosomes whereas bound ribosomes are readily detected on the cytosolic surface of the endoplasmic reticulum

Summary

Gottfried Schatz

Mitochondria import virtually all of their proteins from the cytoplasm This import process faces two unique challenges; the proteins must be routed to their correct submitochondrial compartment, and those destined for the innermost compartment (the matrix) must be transported across two membranes. The eukaryotic cytoplasm contains several different molecular chaperones that bind newly synthesized precursors and prevent their aggregation or irreversible misfolding. These chaperones include members of the 70-kDa heat-shock protein (hsp70) family, which bind non-native proteins targeted to several subcellular compartments. At least one cytosolic chaperone appears dedicated to mitochondrial protein import; the heterodimeric protein termed mitochondrial import stimulating factor (MSF) binds matrix targeting signals [16]. Some small and hydrophilic precursors may well travel through the cytosol without assistance by a chaperone, but this fact has not been clearly established

The Tom Complex

The Tim Complex

Role of the Tim Complex in Protein Sorting

Protein Folding in the Matrix

Evolutionary Origin of the Mitochondrial Protein Import System

The Protein Import System of Mitochondria Gottfried Schatz