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

inner mitochondrial membrane The inner mitochondrial membrane (IMM) is the mitochondrial membrane which separates the mitochondrial matrix from the intermembrane space. Structure The structure of the inner mitochondrial membrane is extensively folded and compartmentalized. T ...

of the

mitochondria A mitochondrion (; ) is an organelle found in the Cell (biology), cells of most Eukaryotes, such as animals, plants and Fungus, fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosi ...

. Components of the TIM complex facilitate the translocation of proteins across the inner membrane and into the

mitochondrial matrix 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, ribo ...

. 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 carriers are proteins from solute carrier family 25 which transfer molecules across the membranes of the mitochondria. Mitochondrial carriers are also classified in thTransporter Classification Database The Mitochondrial Carrier (MC ...

The TIM23 complex

The TIM23 complex facilitates translocation of matrix-targeted proteins into the mitochondrial matrix. 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 proteins, or extrinsic membrane proteins, are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins, or penetrate the periph ...

. 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 is the catabolic reaction process by which chemical energy that has been stored in the high-energy phosphoanhydride bonds in adenosine triphosphate (ATP) is released after splitting these bonds, for example in muscles, by prod ...

. 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, also known as chaperonins (Cpn), is a family of heat shock proteins originally sorted by their 60kDa molecular mass. They prevent misfolding of proteins during stressful situations such as high heat, by assisting protein folding. HSP60 bel ...

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 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 ...

, 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 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 ...

, 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. 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 Mitochondrial import inner membrane translocase subunit Tim23 is an enzyme that in humans is encoded by the ''TIMM23'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of ...

Human proteins containing this domain

TIM17A;

TIMM17A Mitochondrial import inner membrane translocase subunit Tim17-A is an enzyme that in humans is encoded by the ''TIMM17A'' gene. See also * Mitochondria Inner Membrane Translocase * TIMM22 * TIMM23 * TIMM44 Mitochondrial import inner membrane ...

; TIMM17B;

TIMM22 Mitochondrial import inner membrane translocase subunit Tim22 is an enzyme that in humans is encoded by the ''TIMM22'' gene. See also * Mitochondria Inner Membrane Translocase * TIMM17A * TIMM23 * TIMM44 Mitochondrial import inner membrane tran ...

;

References

{{reflist Transport proteins Mitochondrial proteins Transmembrane proteins Protein complexes