PNAs: two sides of mitochondrial protein transport

July 3, 2015 / BIOON / - mitochondria are the energy factories of cells By oxidizing (substrate level phosphorylation) to break down the metabolites of sugars, most of the energy money needed by cells, ATP, is synthesized Therefore, the normal operation of mitochondria is just as important to modern society as oil refineries or power plants The normal work of mitochondria needs a large number of proteins to provide support It is generally believed that the protein content in mitochondria is maintained by the input of newly synthesized proteins and the degradation of old proteins Proteins from the cytoplasm are transported into the intercalation space of the two-layer plasma membrane of the mitochondria, and then the normal folding is completed In this way, the mitochondria can complete the aggregation of proteins Proteins enter the mitochondria with the help of transporters, but how or whether proteins exit the mitochondria has always been in question   The latest research can partly solve the problem of mitochondrial protein transport Researchers in Freiburg, Germany, and Warsaw, Poland, have found a new mechanism for mitochondria to maintain protein quantity stability Generally speaking, the proteins in the cytoplasm need the help of transport proteins to enter the mitochondria There are many large transport channel protein complexes (ToM) on the outer plasma membrane of mitochondria, and the newly synthesized proteins need to go through different paths to enter the mitochondria In the last step of this process, the process of protein entering mitochondria is usually accompanied by the folding of this protein The correct folding mode can ensure that the protein from the cytoplasm can reach the final destination, the intercalation space of the mitochondrial bilayer plasma membrane   New research suggests that protein can not only be maintained in mitochondria, but also be transported out Their experiment found that those proteins that could not fold normally were removed from the mitochondria, which had never been proved before This antiporter (from mitochondria to cytoplasm) has been shown to be related to the reduction of cysteine (disulfide bond breaking) Previous studies have shown that the newly entered mitochondrial proteins are recognized by MIA 40, a key factor for protein aggregation in mitochondrial bilayers Then, the cysteine on the protein entering the mitochondrion is oxidized together with another mitochondrial protein ERV1 in MIA 40 to form a disulfide bond and complete the folding However, the protein that fails to fold correctly will break the cysteine disulfide bond to open the fold, and then transport out the mitochondria with the assistance of other proteins   They also found that smaller proteins could escape mitochondria more efficiently with the help of tom40 At the same time, those proteins that fail to fold properly will be released from mitochondria, and there will be small pieces of degraded proteins in the cytoplasm There are two sides of protein transport in mitochondria Through this reverse transport mechanism, mitochondria can better maintain the dynamic balance of its quantity, thus providing energy for cells stably (BIOON Com)
This article is the original compilation of Biovalley Welcome to reprint! Please indicate the source of the reprint and attach the original link For more information, please download Biovalley information app
doi: 10.1073/pnas.1504615112
PMC:
PMID:
Retro-translocation of mitochondrial intermembrane space proteins
The content of mitochondrial proteome is maintained through two highly dynamic processes, the influx of newly synthesized proteins from the cytosol and the protein degradation Mitochondrial proteins are targeted to the intermembrane space by the mitochondrial intermembrane space assembly pathway that couples their import and oxidative folding The folding trap was proposed to be a driving mechanism for the mitochondrial accumulation of these proteins Whether the reverse movement of unfolded proteins to the cytosol occurs across the intact outer membrane is unknown We found that reduced, conformationally destabilized proteins are released from mitochondria in a size-limited manner We identified the general import pore protein Tom40 as an escape gate We propose that the mitochondrial proteome is not only regulated by the import and degradation of proteins but also by their retro-translocation to the external cytosolic location Thus, protein release is a mechanism that contributes to the mitochondrial proteome surveillance.