TOMM22

What is TOMM22 protein?

TOMM22 gene (translocase of outer mitochondrial membrane 22) is a protein coding gene which situated on the long arm of chromosome 22 at locus 22q13. TOMM22 is an integral membrane protein of the mitochondrial outer membrane. It plays a crucial role in the process of protein import into mitochondria, interacting with other proteins such as TOMM20 and TOMM40 to form a complex that imports cytosolic preproteins into the mitochondrion. This protein is involved in the recognition and translocation of these preproteins and, together with the peripheral receptor TOM20, functions as the transit peptide receptor, facilitating the movement of preproteins into the translocation pore. The TOMM22 protein is consisted of 142 amino acids and TOMM22 molecular weight is approximately 15.5 kDa.

What is the function of TOMM22 protein?

It serves as a central receptor component of the translocase of the outer membrane of mitochondria (TOM complex) and is responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. TOMM22 interacts with other proteins such as TOMM20 and TOMM40 to form a complex that facilitates the movement of preproteins into the translocation pore. This protein is essential for the translocation across the mitochondrial outer membrane of cytochrome P450 monooxygenases and other proteins. Furthermore, TOMM22 has been reported to have chaperone-like activity, helping to maintain substrate preproteins in an unfolded state and preventing them from aggregating on the mitochondrial surface.

Fig1. Sketch hypothesizes a mechanism for impaired mitochondrial homeostasis and mitophagy. (Bojana Kravic, 2018)

TOMM22 Related Signaling Pathway

TOMM22 is a central component of the translocase of the outer mitochondrial membrane (TOM complex), which is responsible for recognizing and translocating cytosolic preproteins into the mitochondria. TOMM22 has been identified as a mitochondrial receptor for the proapoptotic protein Bax. The interaction of Bax with TOMM22 is an essential step in the implementation of apoptosis. TOMM22 is involved in mitophagy, a selective form of autophagy that is responsible for the degradation and recycling of mitochondria, as part of the TOM complex. TOMM22 may also play a role in broader cellular processes such as cell signaling and metabolism, given its involvement in the translocation of proteins that could be involved in these pathways.

TOMM22 Related Diseases

TOMM22 has been associated with several diseases, predominantly those involving mitochondrial dysfunction and cellular metabolism. Notably, mutations in the TOMM22 gene are linked to Myopathy, Centronuclear, 1, a condition characterized by muscle weakness and structural abnormalities in muscle fibers. Furthermore, research has indicated that TOMM22 plays a crucial role in liver cell survival and regeneration models, with mutations leading to liver-specific defects and hepatocyte death post-differentiation. In the context of cancer, TOMM22 has been found to be overexpressed in pancreatic cancer, where it promotes aggressive growth and malignant behavior by modulating mitochondrial protein import and function. Additionally, TOMM22 is implicated in 3-methylglutaconic aciduria types III and V, which are metabolic disorders related to defects in mitochondrial protein translocation.

Bioapplications of TOMM22

TOMM22 is a central component of the TOM complex, which is responsible for recognizing and translocating cytosolic preproteins into mitochondria, making it a key player in studies of mitochondrial biogenesis and protein import mechanisms. TOMM22's involvement in the transport of proteins into mitochondria makes it a potential target for drug delivery systems aimed at modulating mitochondrial function in diseases. The association of TOMM22 with various diseases, including myopathy and pancreatic cancer, suggests its potential as a diagnostic or prognostic biomarker. TOMM22's role in liver cell survival and regeneration models offers a valuable tool for studying liver development, function, and disease.

Case Study 1: Bojana Kravic, 2018

In mammals, the biological function of protein kinase CSNK2/CK2 remains vastly elusive and it is unknown whether CSNK2-dependent phosphorylation of TOMM protein subunits has a similar role as that in yeast. To address this issue, researchers used a skeletal muscle-specific Csnk2b/Ck2β-conditional knockout (cKO) mouse model. Enzymatically, active muscle lysates from skeletal muscle Csnk2b cKO mice phosphorylate murine TOMM22, the mammalian ortholog of yeast Tom22, to a lower extent than lysates prepared from controls. Mechanistically, CSNK2-mediated phosphorylation of TOMM22 changes its binding affinity for mitochondrial precursor proteins. Mitophagy can be normalized by either introduction of a phosphomimetic TOMM22 mutant in cultured myotubes, or by in vivo electroporation of phosphomimetic Tomm22 into muscles of mice. Importantly, transfection of the phosphomimetic Tomm22 mutant in muscle cells with ablated Csnk2b restored their oxygen consumption rate comparable to wild-type levels.

Fig1. In vitro radio-isotope-assisted phosphorylation of TOMM22 is less efficient by muscle lysates.

Fig2. Representative TOMM22 immunoblot images of GST affinity isolations.

Case Study 2: M Yano, 2000

Mitochondria have a receptor complex in the outer membrane which recognizes and translocates mitochondrial proteins synthesized in the cytosol. Researchers report here the identification and functional analysis of human Tom22 (hTom22). hTom22 has an N-terminal negatively charged region exposed to the cytosol, a putative transmembrane region, and a C-terminal intermembrane space region with little negative charge. Tom22 forms a complex with Tom20, and its cytosolic domain functions as an import receptor as in fungi. An import inhibition assay, using pre-ornithine transcarbamylase (pOTC) derivatives and a series of hTom22 deletion mutants, showed that the C-terminal segment of the cytosolic domain is important for presequence binding, whereas the N-terminal domain is important for binding to the mature portion of pOTC. No evidence for pOTC interaction with the Tom22 intermembrane space domain was obtained. Binding studies revealed that the presequence is critical for pOTC binding to Tom20, whereas both the presequence and mature portion are important for binding to Tom22. A cell-free immunoprecipitation assay indicated that an internal segment of the Tom22 cytosolic domain is important for interaction with Tom20.

Fig3. The cell extract was subjected to SDS–12% PAGE and immunoblot analysis using affinity-purified antibodies.

Fig4. COS-7 cells were transfected with 10 μg of pCAGGS (control) or pCAGGS-hTom22.

TOMM22 has several biochemical functions, for example, protein binding,contributes_to protein channel activity,protein transmembrane transporter activity. Some of the functions are cooperated with other proteins, some of the functions could acted by TOMM22 itself. We selected most functions TOMM22 had, and list some proteins which have the same functions with TOMM22. You can find most of the proteins on our site.

TOMM22 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with TOMM22 here. Most of them are supplied by our site. Hope this information will be useful for your research of TOMM22.

PTP4A3;TOMM40;TOMM7;PHLDA3;PAPD5;XRCC3;ILK;Rmdn3;P;Cdc26;PCDHB15