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. The electron transport chain is located on the inner membrane of the mitochondria...

 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 cells, in which more specialized structures are embedded, and a specific part of the mitochondrion that is the site of oxidation of organic molecules. The internal structure of connective tissues is an extracellular 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.

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 catalyze the oxidation of pyruvate and other small organic molecules.The mitochondrial matrix also contains the mitochondria's DNA and ribosomes. The word "matrix" stems from the fact that this space is viscous, compared to the...

. 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. The regulatory protein subunits of many ion channels and...

. 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 phosphoanhydridic bonds in ATP is released, for example in the muscles, to produce work. The product is ADP and an inorganic phosphate, orthophosphate...

. 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 to allow movement of proteins through this barrier and into the intermembrane space of the mitochondrion. Most of the proteins needed for mitochondrial...

, 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 also known as IMS 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.

Subfamilies

• Mitochondrial import inner membrane translocase, subunit TIMM17 
• Mitochondrial import inner membrane translocase, subunit TIMM23
  TIMM23
  Mitochondrial import inner membrane translocase subunit Tim23 is an enzyme that in humans is encoded by the TIMM23 gene.-Further reading:...
  
   

Human proteins containing this domain

TIM17A; TIMM17A

TIMM17A

Mitochondrial import inner membrane translocase subunit Tim17-A is an enzyme that in humans is encoded by the TIMM17A gene.-Further reading:...

; TIMM17B; TIMM22

TIMM22

Mitochondrial import inner membrane translocase subunit Tim22 is an enzyme that in humans is encoded by the TIMM22 gene.-Further reading:...

; TIMM23

TIMM23

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

;