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Translocase of the inner membrane

 

 
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Translocase of the inner membrane
 
 
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The translocase of the inner membrane (TIM) is a complex of proteins found in the inner mitochondrial membrane
Inner mitochondrial membrane

The mitochondrial inner membrane forms internal compartments known as cristae, which allow greater space for the proteins such as cytochromes to function properly and efficiently....
 of the mitochondria. Components of the TIM complex facilitate the translocation of proteins across the inner membrane and into the matrix (biology)
Matrix (biology)

In biology, matrix is the material between animal or plant cell , the material in which more specialized structures are embedded, and a specific part of the mitochondrion that is the site of oxidation of organic molecules....
. 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
Mitochondrial carrier family of proteins

Carrier protein structure and functionThe transport of metabolites in and out of the mitochondrial matrix is controlled at the level of the inner mitochondrial membrane....
.

TIM23 complex facilitates translocation of matrix-targeted proteins, into the mitochondrial matrix
Mitochondrial matrix

In the mitochondrion, the matrix contains soluble enzymes that catalysis the oxidation of pyruvic acid and other small organic molecules.The mitochondrial matrix also contains the mitochondria's DNA and ribosomes....
.






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The translocase of the inner membrane (TIM) is a complex of proteins found in the inner mitochondrial membrane
Inner mitochondrial membrane

The mitochondrial inner membrane forms internal compartments known as cristae, which allow greater space for the proteins such as cytochromes to function properly and efficiently....
 of the mitochondria. Components of the TIM complex facilitate the translocation of proteins across the inner membrane and into the matrix (biology)
Matrix (biology)

In biology, matrix is the material between animal or plant cell , the material in which more specialized structures are embedded, and a specific part of the mitochondrion that is the site of oxidation of organic molecules....
. 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
Mitochondrial carrier family of proteins

Carrier protein structure and functionThe transport of metabolites in and out of the mitochondrial matrix is controlled at the level of the inner mitochondrial membrane....
.

The TIM23 complex

The TIM23 complex facilitates translocation of matrix-targeted proteins, into the mitochondrial matrix
Mitochondrial matrix

In the mitochondrion, the matrix contains soluble enzymes that catalysis the oxidation of pyruvic acid and other small organic molecules.The mitochondrial matrix also contains the mitochondria's DNA and ribosomes....
. These proteins contain a cleavable presequence. The TIM23 complex is made up of the subunits Tim17, Tim21 and Tim23, which are thought to contribute to the structural formation of the translocation channel that spans the inner membrane, and Tim44, which is a peripheral membrane protein
Peripheral membrane protein

Peripheral membrane proteins are proteins that adhere only temporarily to the biological membrane with which they are associated. These molecules attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer....
. Tim44 is only weakly associated with Tim23 and is located on the matrix side of the inner membrane. At the opening of the TIM17-23 complex, Tim44 recruits mitochondrial heat shock protein 70, which further mediates translocation of the precursor through ATP hydrolysis
ATP hydrolysis

ATP hydrolysis is the reaction by which chemical energy that has been stored and transported in the High energy phosphate in adenosine triphosphate is released, for example in the muscles, to produce work....
. Following protein entry into the matrix, the presequence is cleaved off by the matrix processing peptidase and the protein undergoes folding into an active conformation, facilitated by HSP60
HSP60

Heat shock proteins are generally responsible for preventing damage to proteins in response to high levels of heat. Heat shock proteins are classified into six major families based on their molecular mass: small HSPs, HSP40, HSP60, HSP70, HSP90, and HSP110...
.

The TIM22 complex

The TIM22 complex is responsible for mediating the integration of carrier preproteins into the inner membrane. Tim22, a subunit of the TIM22 complex, forms a channel within the inner membrane and is referred to as the carrier translocase. Tim54 and the small Tim proteins, Tim9, Tim10 and Tim12 also contribute to the TIM22 complex as well as Tim18. The function of Tim18 is not yet clear; however it is believed to play a role in assembly and stabilisation of the TIM22 complex, although is not involved in protein insertion into the membrane. Tim54, although it does not associate directly with Tim22, is also believed to assist in the stability of Tim22. Unlike cleavable preproteins, following translocation across the outer membrane via the translocase of the outer membrane
Translocase of the outer membrane

The translocase of the outer membrane is a complex of proteins found in the outer mitochondrial membrane of the mitochondria. Its function is allow movement of proteins through this barrier and into the intermembrane space of the mitochondrion....
, carrier preproteins are bound by the soluble Tim9-Tim10 complex of which the majority of this complex (~95%) is free floating within the intermembrane space
Intermembrane space

The intermembrane space is the region between the inner membrane and the outer membrane of a mitochondrion or a chloroplast. The main function of the intermembrane space is oxidative phosphorylation....
. It is possible that this small Tim complex is able to stabilise precursor carrier proteins by acting as a chaperone and preventing the hydrophobic precursors from aggregating in the aqueous environment of the intermembrane space. A small portion of Tim9 and Tim10 (~5%) assembles into a modified complex containing Tim12, on the outer surface of the TIM22 complex. Tim12 is membrane bound and thus may act as a linker molecule docking Tim9 and Tim10 to the face of the TIM22 complex. The carrier preprotein is then inserted into the inner mitochondrial membrane in a potential-dependent fashion. The membrane potential is necessary for both insertion of the precursor into the carrier translocase and lateral release of the protein into the lipid phase of the inner mitochondrial membrane, which completes protein translocation. However this membrane potential-dependent process takes place in absence of ATP-driven machinery.

See also

Sorting and assembly machinery
Sorting and assembly machinery

The outer mitochondrial membrane is made up of two essential proteins, Tom40 and Sam50.Tom40 is an protein import pore required for the import of precursor proteins across the outer mitochondrial membrane and it makes up part of the translocase of the outer membrane....