Translocase of the outer membrane

Last updated
Mitochondrial import receptor subunit TOM20
PBB Protein TOMM20 image.jpg
Identifiers
SymbolTOM20_plant
Pfam PF06552
InterPro IPR010547
TCDB 3.A.8
OPM superfamily 266
OPM protein 3awr
Membranome 170
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
TOM7 family
Identifiers
SymbolTom7
Pfam PF08038
InterPro IPR012621
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Mitochondrial import receptor subunit Tom22
Identifiers
SymbolTom22
Pfam PF04281
InterPro IPR005683
TCDB 3.A.8
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary

The translocase of the outer membrane (TOM) is a complex of proteins found in the outer mitochondrial membrane of the mitochondria. It allows movement of proteins through this barrier and into the intermembrane space of the mitochondrion. Most of the proteins needed for mitochondrial function are encoded by the nucleus of the cell. The outer membrane of the mitochondrion is impermeable to large molecules greater than 5000 daltons. [1] The TOM works in conjunction with the translocase of the inner membrane (TIM) to translocate proteins into the mitochondrion. Many of the proteins in the TOM complex, such as TOMM22, were first identified in Neurospora crassa and Saccharomyces cerevisiae . [2] Many of the genes encoding these proteins are designated as TOMM (translocase of the outer mitochondrial membrane) complex genes.

Contents

The complete mitochondrial protein translocase complex includes at least 19 proteins: several chaperones, four proteins of the outer membrane translocase (Tom) import receptor, five proteins of the Tom channel complex, five proteins of the inner membrane translocase (Tim) and three "motor" proteins.

Protein targeting to the mitochondria

There are various mitochondrial import pathways that exist to facilitate the import of precursor proteins to their destined mitochondrial subcompartments. HSP90 aids the delivery of the mitochondrial preprotein to the TOM complex in an ATP-dependent process. [3] Many precursor proteins (those that are destined for the matrix) contain amino-terminal presequences that carry information required for the targeting of proteins to the mitochondrial matrix [4] These matrix targeting signals generally contain 10-80 amino acid residues that take on the conformation of an amphipathic-α helix [5] and contain one positive and hydrophobic face. Once the precursor reaches the matrix, the presequence is typically cleaved off by the matrix processing peptidase. [6] Proteins targeted to other sub-compartments of the mitochondria such as the intermembrane space and inner mitochondrial membrane, contain internal targeting signals, these signals have an indefinable nature and are inconsistent in their pattern. Proteins targeted to the outer membrane also contain internal targeting signals, not all of which have been identified, and include proteins that take on a β-barrel structure, [7] such as Tom40. Some proteins however, that are targeted to the outer mitochondrial membrane contain a hydrophobic tail domain that anchors the protein to the membrane. [8]

Members of the complex

The translocase of the outer membrane (TOM) forms a complex made of Tom70, Tom22, and Tom20, along with Tom40, Tom7, Tom6, and Tom5. Tom20 and Tom22 are preprotein receptors, which are responsible for recognition of the cleavable presequence possessed by mitochondrial-targeted proteins. [9] Tom70 is also a preprotein receptor and may recognise some cleavable presequence proteins, however it is mainly responsible for the recognition of non-cleavable preproteins and acts as a point for chaperone binding. [6] [10] Tom22 is anchored to the outer membrane by a single transmembrane segment and also plays a role in stabilizing the TOM complex. [11] Tom40 is the core element of the translocase complex and complexes with Tom22 with a mass of approximately 350 kilodaltons. [12] It forms the central protein-conducting channel with a diameter of approximately 2.5 nm. [12] The human Tom22 is approximately 15.5 kilodaltons and complexes with Tom20. [13] The N-terminal end of Tom22 extends into the cytosol and is involved in preprotein binding. [13]

Human proteins

TOMM22, TOMM40, TOM7, TOMM7

See also

Related Research Articles

Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the cell. Proteins can be targeted to the inner space of an organelle, different intracellular membranes, the plasma membrane, or to the exterior of the cell via secretion. Information contained in the protein itself directs this delivery process. Correct sorting is crucial for the cell; errors or dysfunction in sorting have been linked to multiple diseases.

<span class="mw-page-title-main">Mitochondrial matrix</span> Space within the inner membrane of the mitochondrion

In the mitochondrion, the matrix is the space within the inner membrane. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitochondrial matrix contains the mitochondrial DNA, ribosomes, soluble enzymes, small organic molecules, nucleotide cofactors, and inorganic ions.[1] The enzymes in the matrix facilitate reactions responsible for the production of ATP, such as the citric acid cycle, oxidative phosphorylation, oxidation of pyruvate, and the beta oxidation of fatty acids.

<span class="mw-page-title-main">Intermembrane space</span>

The intermembrane space (IMS) is the space occurring between or involving two or more membranes. In cell biology, it is most commonly described as the region between the inner membrane and the outer membrane of a mitochondrion or a chloroplast. It also refers to the space between the inner and outer nuclear membranes of the nuclear envelope, but is often called the perinuclear space. The IMS of mitochondria plays a crucial role in coordinating a variety of cellular activities, such as regulation of respiration and metabolic functions. Unlike the IMS of the mitochondria, the IMS of the chloroplast does not seem to have any obvious function.

<span class="mw-page-title-main">TIM/TOM complex</span>

The TIM/TOM complex is a protein complex in cellular biochemistry which translocates proteins produced from nuclear DNA through the mitochondrial membrane for use in oxidative phosphorylation. In enzymology, the complex is described as an mitochondrial protein-transporting ATPase, or more systematically ATP phosphohydrolase , as the TIM part requires ATP hydrolysis to work.

<span class="mw-page-title-main">Mitochondrial membrane transport protein</span>

Mitochondrial membrane transport proteins, also known as mitochondrial carrier proteins, are proteins which exist in the membranes of mitochondria. They serve to transport molecules and other factors, such as ions, into or out of the organelles. Mitochondria contain both an inner and outer membrane, separated by the inter-membrane space, or inner boundary membrane. The outer membrane is porous, whereas the inner membrane restricts the movement of all molecules. The two membranes also vary in membrane potential and pH. These factors play a role in the function of mitochondrial membrane transport proteins. There are 53 discovered human mitochondrial membrane transporters, with many others that are known to still need discovered.

Translocase is a general term for a protein that assists in moving another molecule, usually across a cell membrane. These enzymes catalyze the movement of ions or molecules across membranes or their separation within membranes. The reaction is designated as a transfer from “side 1” to “side 2” because the designations “in” and “out”, which had previously been used, can be ambiguous. Translocases are the most common secretion system in Gram positive bacteria.

<span class="mw-page-title-main">TIMM8A</span> Protein-coding gene in humans

Mitochondrial import inner membrane translocase subunit Tim8 A, also known as deafness-dystonia peptide or protein is an enzyme that in humans is encoded by the TIMM8A gene. This translocase has similarity to yeast mitochondrial proteins that are involved in the import of metabolite transporters from the cytoplasm into the mitochondrial inner membrane. The gene is mutated in deafness-dystonia syndrome and it is postulated that MTS/DFN-1 is a mitochondrial disease caused by a defective mitochondrial protein import system.

<span class="mw-page-title-main">TOMM20</span> Protein-coding gene in the species Homo sapiens

Mitochondrial import receptor subunit TOM20 homolog is a protein that in humans is encoded by the TOMM20 gene. TOM20 is one of the receptor systems of the translocase of the outer membrane (TOM) complex in the outer mitochondrial membrane.

<span class="mw-page-title-main">TOMM22</span> Protein-coding gene in the species Homo sapiens

Mitochondrial import receptor subunit TOM22 homolog(hTom22) is a protein that in humans is encoded by the TOMM22 gene.

<span class="mw-page-title-main">TOMM34</span> Protein-coding gene in the species Homo sapiens

Mitochondrial import receptor subunit TOM34 is a protein that in humans is encoded by the TOMM34 gene.

<span class="mw-page-title-main">TIMM10</span> Protein-coding gene in the species Homo sapiens

Mitochondrial import inner membrane translocase subunit Tim10 is an enzyme that in humans is encoded by the TIMM10 gene.

<span class="mw-page-title-main">TIMM10B</span> Protein-coding gene in the species Homo sapiens

Mitochondrial import inner membrane translocase subunit Tim9 B is an enzyme that in humans is encoded by the FXC1 gene.

<span class="mw-page-title-main">TOMM70</span> Protein-coding gene in the species Homo sapiens

Mitochondrial import receptor subunit TOM70, also known as translocase of outer mitochondrial membrane protein 70 is a protein that in humans is encoded by the TOMM70 gene.

<span class="mw-page-title-main">TIMM23</span> Protein-coding gene in the species Homo sapiens

Mitochondrial import inner membrane translocase subunit Tim23 is an enzyme that in humans is encoded by the TIMM23 gene.

<span class="mw-page-title-main">TOMM40</span> Protein-coding gene in the species Homo sapiens

Mitochondrial import receptor subunit TOM40 homolog is a protein which in humans is encoded by the TOMM40 gene.

<span class="mw-page-title-main">TIMM9</span> Protein-coding gene in the species Homo sapiens

Mitochondrial import inner membrane translocase subunit Tim9 is an enzyme that in humans is encoded by the TIMM9 gene.

The translocase of the inner membrane (TIM) is a complex of proteins found in the inner membrane of the mitochondrion. Components of the TIM complex facilitate the translocation of proteins across the inner membrane and into the mitochondrial matrix. They also facilitate the insertion of proteins into the inner mitochondrial membrane, where they must reside in order to function, these mainly include members of the mitochondrial carrier family of proteins.

Tim9 and Tim10 make up the group of essential small Tim proteins that assist in transport of hydrophobic precursors across the intermembrane space in mammalian cells. Both Tim9 and Tim10 form a hexamer, the Tim9-Tim10 complex, that when associated, functions as a chaperone to assist translocation of preproteins from the outer mitochondrial membrane to the translocase of the inner membrane. The functional Tim9-Tim10 complex not only directs preproteins to the inner mitochondrial membrane in order to interact with the TIM22 complex, but also guides β-barrel precursor proteins to the sorting and assembly machinery (SAM) of the outer membrane.

The outer mitochondrial membrane is made up of two essential proteins, Tom40 and Sam50.

Mitochondrial processing peptidase is an enzyme complex found in mitochondria which cleaves signal sequences from mitochondrial proteins. In humans this complex is composed of two subunits encoded by the genes PMPCA, and PMPCB. The enzyme is also known as. This enzyme catalyses the following chemical reaction

References

  1. ↑ Alberts, Bruce; Alexander Johnson; Julian Lewis; Martin Raff; Keith Roberts; Peter Walter (1994). Molecular Biology of the Cell . New York: Garland Publishing Inc. ISBN   978-0-8153-3218-3.
  2. ↑ Seki N, Moczko M, Nagase T, et al. (1996). "A human homolog of the mitochondrial protein import receptor Mom19 can assemble with the yeast mitochondrial receptor complex". FEBS Lett. 375 (3): 307–10. doi:10.1016/0014-5793(95)01229-8. PMID   7498524.
  3. ↑ Humphries AD, Streimann IC, Stojanovski D, Johnston AJ, Yano M, Hoogenraad NJ, Ryan MT (March 2005). "Dissection of the mitochondrial import and assembly pathway for human Tom40". J Biol Chem. 280 (12): 11535–43. doi: 10.1074/jbc.M413816200 . PMID   15644312.
  4. ↑ Saitoh T, Igura M, Obita T, Ose T, Kojima R, Maenaka K, Endo T, Kohda D (November 2007). "Tom20 recognizes mitochondrial presequences through dynamic equilibrium among multiple bound states". EMBO J. 26 (22): 4777–87. doi:10.1038/sj.emboj.7601888. PMC   2080804 . PMID   17948058.
  5. ↑ Tokatlidis K, Vial S, Luciano P, Vergnolle M, Clémence S (2000). "Membrane protein import in yeast mitochondria". Biochem. Soc. Trans. 28 (4): 495–9. doi:10.1042/0300-5127:0280495. PMID   10961947.
  6. 1 2 Young JC, Hoogenraad NJ, Hartl FU (January 2003). "Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70". Cell. 112 (1): 41–50. doi: 10.1016/S0092-8674(02)01250-3 . PMID   12526792.
  7. ↑ Bolender N, Sickmann A, Wagner R, Meisinger C, Pfanner N (January 2008). "Multiple pathways for sorting mitochondrial precursor proteins". EMBO Rep. 9 (1): 42–9. doi:10.1038/sj.embor.7401126. PMC   2246611 . PMID   18174896.
  8. ↑ Koehler CM, Merchant S, Schatz G (November 1999). "How membrane proteins travel across the mitochondrial intermembrane space". Trends Biochem. Sci. 24 (11): 428–32. doi:10.1016/S0968-0004(99)01462-0. PMID   10542408.
  9. ↑ Ryan MT, Müller H, Pfanner N (July 1999). "Functional staging of ADP/ATP carrier translocation across the outer mitochondrial membrane". J. Biol. Chem. 274 (29): 20619–27. doi: 10.1074/jbc.274.29.20619 . PMID   10400693.
  10. ↑ Asai T, Takahashi T, Esaki M, Nishikawa S, Ohtsuka K, Nakai M, Endo T (May 2004). "Reinvestigation of the requirement of cytosolic ATP for mitochondrial protein import". J. Biol. Chem. 279 (19): 19464–70. doi: 10.1074/jbc.M401291200 . PMID   15001571.
  11. ↑ Endres M, Neupert W, Brunner M (June 1999). "Transport of the ADP/ATP carrier of mitochondria from the TOM complex to the TIM22.54 complex". EMBO J. 18 (12): 3214–21. doi:10.1093/emboj/18.12.3214. PMC   1171402 . PMID   10369662.
  12. 1 2 Ahting U, Thieffry M, Engelhardt H, Hegerl R, Neupert W, Nussberger S (2001). "Tom40, the Pore-Forming Component of the Protein-Conducting Tom Channel in the Outer Membrane of Mitochondria". J. Cell Biol. 153 (6): 1151–60. doi:10.1083/jcb.153.6.1151. PMC   2192023 . PMID   11402060.
  13. 1 2 Yano M, Hoogenraad N, Terada K, Mori M (2000). "Identification and Functional Analysis of Human Tom22 for Protein Import into Mitochondria". Mol Cell Biol. 20 (19): 7205–13. doi:10.1128/MCB.20.19.7205-7213.2000. PMC   86274 . PMID   10982837.
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