Translocase of the outer membrane

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]

Mitochondrial import receptor subunit TOM20
Identifiers
SymbolTOM20_plant
PfamPF06552
InterProIPR010547
TCDB3.A.8
OPM superfamily266
OPM protein3awr
Membranome170
TOM7 family
Identifiers
SymbolTom7
PfamPF08038
InterProIPR012621
Mitochondrial import receptor subunit Tom22
Identifiers
SymbolTom22
PfamPF04281
InterProIPR005683
TCDB3.A.8

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 350k Daltons.[12] It forms the central protein-conducting channel with a diameter of approximately 2.5 nm.[12] The human Tom22 is approximately 15.5k Daltons 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

gollark: This was before floating pointers, sadly.
gollark: ```c#include <stdint.h>#include <stddef.h>static uintptr_t MEMPOS = 1;void* malloc(size_t size) { uintptr_t bees = MEMPOS; MEMPOS += size; return (void*)bees;}void free(void* ptr) { *(char**)ptr = "hello please do not use this address";}```
gollark: I'm sure I'll find it eventually.
gollark: It's classified.
gollark: I already wrote malloc and came up with the floating pointers idea.

See also

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. 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. 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. 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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