protein insertion into mitochondrial outer membrane

Definition

Target type: biologicalprocess

The process comprising the insertion of proteins from outside the organelle into the mitochondrial outer membrane, mediated by large outer membrane translocase complexes. [GOC:mcc, GOC:vw, PMID:18672008]

The insertion of proteins into the mitochondrial outer membrane (MOM) is a complex and tightly regulated process that ensures the proper localization and function of these proteins within the organelle. The MOM, unlike the inner membrane, is permeable to small molecules but acts as a barrier for larger proteins and macromolecules. This selective permeability is crucial for maintaining the distinct composition of the mitochondrial matrix and intermembrane space.

The majority of proteins targeted to the MOM are synthesized in the cytosol and contain specific targeting signals that guide them to their destination. These signals, often referred to as mitochondrial targeting sequences (MTSs), are typically located at the N-terminus of the protein. The MTS typically consists of a stretch of positively charged amino acids followed by a hydrophobic region. This structure is recognized by chaperone proteins in the cytosol, particularly the heat shock protein 70 (Hsp70) family, which prevent the newly synthesized proteins from misfolding and aggregation.

Once the protein-Hsp70 complex reaches the MOM, it interacts with the translocase of the outer membrane (TOM) complex. The TOM complex is a multi-protein channel that acts as a gatekeeper for protein import into mitochondria. The TOM complex recognizes and binds to the MTS of the incoming protein, facilitating its passage through the MOM.

The TOM complex consists of several subunits, each playing a specific role in the translocation process. TOM20 and TOM22 are receptor proteins that bind the MTS. TOM40 is the pore-forming subunit that allows the protein to traverse the membrane. Other subunits, such as TOM5, TOM6, and TOM7, provide structural support and regulate the activity of the complex.

The process of protein insertion into the MOM can be divided into two main pathways:

1. **The "Stop-Transfer" Pathway:** This pathway is used for proteins that are destined for the intermembrane space or the inner membrane. The MTS is cleaved by a protease located in the intermembrane space, leaving a mature protein that is anchored to the MOM by a transmembrane domain.

2. **The "β-Barrel Insertion" Pathway:** This pathway is used for proteins that form β-barrel structures, a common motif found in MOM proteins. These proteins contain a signal sequence that directs them to the TOM complex, but they also have a second signal sequence that is recognized by the β-barrel assembly machinery (BAM) complex. The BAM complex is another multi-protein complex that facilitates the folding and insertion of β-barrel proteins into the MOM.

Once the protein has been inserted into the MOM, it may undergo further modifications, such as folding, assembly into protein complexes, or phosphorylation. These modifications are essential for the proper functioning of the protein within the mitochondrial context.

In summary, protein insertion into the MOM is a tightly regulated process that involves specific targeting signals, chaperone proteins, and specialized protein complexes, including the TOM and BAM complexes. The process ensures the precise localization and proper function of these proteins, contributing to the overall functionality of the mitochondria and the cell.'
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Proteins (1)

Compounds (60)