Translocase of the outer membrane

Figure 3. Schematic architecture of mitochondrial protein complexes. A transmembrane channel, called the permeability transition pore (FTP), is formed at the contaa sites between the inner and outer mitochondrial membrane (OM) of the mitochondria. The core components of PTP are the voltage-dependent anion channel (VDAC) in the outer membrane and the adenine nucleotide translocator (ANT) in the inner membrane (IM). VDAC allows diilusion of small molecules (<5 kDa), however ANT is only permeable to a few selected ions and metabolites and is responsible for maintaining the proton concentration gradient (pH) and the membrane elearic potential (A P,J. PTP is sometimes connected to destruction of permeability barrier and loss of the inner membrane potential and eventually results in mitochondrial membrane permeability transition during apoptosis and other specialized forms of cell death. Bax, Bak, Bc1-Xl and Bcl-2 locate in the outer membrane and may regulate the outer membrane permeability. The translocase of the outer membrane (TOM) and the translocase of the inner membrane (TlM) mediate protein import pathway in the mitochondria. Cy-D, cyclophilin D PBR, peripheral benzodiazepine receptor HK, hexokinase mtHSP70, mitochondrial heat shock protein 70.

Becker L et al. (2005) Preprotein translocase of the outer mitochondrial membrane reconstituted Tom40 forms a characteristic TOM pore. J Mol Biol 353 1011-1020 Blobel G, Dobberstein (1975a) Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma. J Cell Biol 67 835-851 Blobel G, Dobberstein (1975b) Transfer to proteins across membranes. II. Reconstitution of functional rough microsomes from heterologous components. J Cell Biol 67 852-862... 

The majority of mitochondria-destined preproteins seem to be imported after completion of polypeptide synthesis (Pfanner et al., 1997 Herrmann and Neupert, 2000). Preproteins are targeted to the outer membrane, often via N-terminal signals, where they bind to translo-case components of the outer membrane (TOM). Preproteins subsequently translocate across the general import pore (Ryan and Pfanner, 1998). Extra complexity is introduced into matrix-imported preproteins because they must also translocate across the inner membrane (Fig. 2). This is achieved via interactions of the preproteins with the translocase... 

Fig. 20.20. Model for the import of nuclear-encoded proteins into the mitochondrial matrix. The matrix preprotein with its positively charged N-terminal presequence is shown in blue. Abbreviations OM, outer mitochondrial membrane IMS, intramembrane space IM, inner mitochondrial membrane TOM, translocases of the outer mitochondrial membrane TIM, translocases of the inner mitochondrial membrane mthspTO, mitochondrial heat shock protein 70.

Whereas the mitochondrial enzymes of p-oxidation reside within the area bound by inner membrane, activation of fatty acids proceeds largely at sites exterior to this membrane. The transport of activated acyl groups across the inner mitochondrial membrane Is brought about by a carnitine dependent route (Fritz, 1963 Bremer, 1968 Bressler, 1970). A carnitine acyltransferase localized on the outer aspect of inner membrane utilizes cytosolic free carnitine to convert the cytosolic acyl-CoA to cytosolic acylcarnitine (Fig. 1). A translocase of the inner membrane then moves the acylcarnitine inside in exchange for the simultaneous movement of carnitine in the opposite direction. Another carnitine acyltransferase, situated on the inner side of the inner membrane, utilizes matrix CoA to convert acylcarnitine to acyl-CoA, thus producing the latter in the same compartment where enzymes of the p-oxidation spiral exist (Pande, 1975 Ramsay and Tubbs, 1975 Tubbs and... 

The outer protein-phospholipidic mitochondrial membrane contains a large number of integral proteins called porins, which form channels that allow relatively small molecules (5,000 Da or less in molecular mass) to freely diffuse from one side of the membrane to the other. Larger proteins are transferred by the protein of the outer membrane called translocase which binds a signaling sequence at their N-terminus, and actively moves them across the membrane. ... 

The transport is accomplished with the participation of carnitine, which takes up the acyl from acyl-CoA on the outer membrane side. Acylcamitine assisted by carnitine translocase diffuses to the inner side of the membrane to give its acyl to the CoA located in the matrix. The process of reversible acyl transfer between CoA and carnitine on the outer and inner sides of the membrane is effected by the enzyme acyl-CoA-camitine transferase. 

FIGURE 31-7 Mitochondrial carriers. Ions and small molecules enter the intermembrane space, since the outer mitochondrial membrane is not a significant permeability barrier. However, the inner mitochondrial membrane is impermeable to ions except those for which there are specific carriers. Most of the carriers are reversible, as indicated by two-headed arrows. Compounds transported in one direction are indicated in red. The ATP/ADP translocase and the aspartate-glutamate carrier are both electrophoretic their transport is driven in the direction of the mitochondrial membrane potential, as indicated by red arrows. Glutamine is carried into the matrix by an electroneutral carrier. The unimpaired functioning of mitochondrial carriers is essential for normal metabolism. (Adapted with permission from reference [70].)... 

There are several hypotheses for a specific mechanism by which ONOO- can control the open state of the PTPC. Briefly the PTPC is regulated by primary constituents of the pore, including the inner membrane adenine nucleotide translocase (ANT) and the outer membrane protein voltage-dependent anion channel (VDAC or porin). The VDAC-ANT complex can bind to signaling proteins that modulate permeability transition, such as pro-apoptotic Bax (which opens the pore) and anti-apoptotic Bcl-2... 

Figure 7.11 Mechanism of transport of long-chain fatty adds across the inner mitochondrial membrane as fatty acyl carnitine. CRT is the abbreviation for carnitine palmitoyl transferase. CPT-I resides on the outer surface of the inner membrane, whereas CPT-II resides on the inner side of the inner membrane of the mitochondria. Transport across the inner membrane is achieved by a carrier protein known as a translocase. FACN - fatty acyl carnitine, CN - carnitine. Despite the name, CRT reacts with long-chain fatty acids other than palmitate. CN is transported out of the mitochondria by the same translocase.

The insertion and assembly of -barrel outer membrane proteins, including Tom40, are assisted by the sorting and assembly machinery (SAM) complex (Fig. 1). The SAM complex consists of four subunits, the core translocase Sam50, which is itself a putative -barrel protein (Kozjak et al. 2003 Paschen et al. 2003 Gentle et al. 2004), and the additional proteins Sam35,... 

Fig-i Mitochondrial protein import machinery as defined in S. cerevisiae. TOM translo-case of the outer mitochondrial membrane SAM sorting and assembly machinery TIM translocase of the inner mitochondrial membrane MIA mitochondrial IMS import and assembly machine PAM presequence translocase associated motor IMP inner membrane protease MPP mitochondrial processing peptidase. The numbers on the individual Tom, Sam, Tim or Pam components represent their approximate molecular masses in kDa. See text for mechanistic details. Adopted from Dolezal et al. 2006... 

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