Mitochondria protein import

A variety of protein import pathways into the vacuole are known (Burd et al., 1998 Bryant and Stevens, 1998). It includes the sorting from the Golgi apparatus, endocytosis, autophagy (where a part of the cytoplasm such as a mitochondrion is engulfed into a newly formed vacuole and is degraded), direct import from the cytosol, and the vacuolar inheritance from the mother cell. Of these, the pathways from the Golgi... 

It is important to appreciate that this principle of coupling-in-series underlies all biochemical pathways or processes, e.g. glycolysis, generation of ATP in the mitochondrion, protein synthesis from amino acids or a signal transduction pathway. Indeed, despite the fundamental importance of signalling pathways in biochemistry, a thermodynamic analysis of such a pathway has never been done, but the principles outlined above must apply even to signalling pathways. 

This zinc-dependent enzyme [EC 3.4.24.59] of the peptidase M3 family catalyzes the hydrolysis of a peptide bond such that there is a release of an N-terminal octa-peptide at the second stage of processing of some proteins imported into the mitochondrion. The natural substrates are precursor proteins that already have been processed by the mitochondrial processing peptidase. 

Regoes A, Zourmpanou D, Leon-Avila G, van der Giezen M, Tovar J, Hehl AB (2005) Protein import, replication and inheritance of a vestigial mitochondrion. J Biol Chem 280 30557-30563... 

Figure 16-26 presents an overview of protein import from the cytosol into the mitochondrial matrix, the route into the mitochondrion followed by most imported proteins. We will discuss in detail each step in protein transport into the matrix... 

After synthesis In the cytosol, the soluble precursors of mitochondrial proteins (Including hydrophobic Integral membrane proteins) interact directly with the mitochondrial membrane. In general, only unfolded proteins can be imported Into the mitochondrion. Chaperone proteins such as cytosolic Hsc70 keep nascent and newly made proteins in an unfolded state, so that they can be taken up by mitochondria. Import of an unfolded mitochondrial precursor is initiated by the binding of a mitochondrial targeting sequence to an import receptor in the outer mitochondrial membrane. These receptors were first identified by experiments in which antibodies to specific proteins of the outer mitochondrial membrane were shown to inhibit protein import into... 

Mitochondria have their own DNA (mtDNA) and genetic continuity. This DNA only encodes 13 peptide subunits synthesized in the matrix that are components of complexes I, III, IV, and V of the respiratory chain. Most mitochondrial proteins are synthesized on cytoplasmic ribosomes and imported by specific mechanisms to their specific locations in the mitochondrion (see below). 

Ered Sanger, a double Nobel Prize winner, sequenced the human mitochondrial genome back in 1981. This genome codes for 13 proteins and the mitochondrion possesses the genetic machinery needed to synthesize them. Thus, the mitochondria are a secondary site for protein synthesis in eukaryotic cells. It turns out that the 13 proteins coded for by the mitochondrial genome and synthesized in the mitochondria are critically important parts of the complexes of the electron transport chain, the site of ATP synthesis. The nuclear DNA codes for the remainder of the mitochondrial proteins and these are synthesized on ribosomes, and subsequently transported to the mitochondria. 

Protein trafficking has been extensively studied in fungi and mammals, and a number of elaborate machines have been described that specifically import certain proteins into typical eukaryotic organelles such as the nucleus, the endoplasmic reticulum and the mitochondrion. 

Mitochondria arise by division and growth of preexisting mitochondria. Because they synthesize only a few proteins and RNA molecules, they must import many proteins and other materials from the cytoplasm. A mitochondrion contains at least 100 proteins that are encoded by nuclear genes.50,50a The mechanisms by which proteins are taken up by mitochondria are complex and varied. Many of the newly synthesized proteins carry, at the N terminus, presequences that contain mitochondrial targeting signals51-53 (Chapter 10). These amino acid sequences often lead the protein to associate with receptor proteins on the outer mitochondrial membrane and subsequently to be taken up by the mitochondria. While the targeting sequences are usually at the N terminus of a polypeptide, they are quite often internal. The N-terminal sequences are usually removed by action of the mitochondrial processing peptidase (MPP) in... 

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