Alternative titles; symbols
HGNC Approved Gene Symbol: TOMM6
Cytogenetic location: 6p21.1 Genomic coordinates (GRCh38): 6:41,787,694-41,789,895 (from NCBI)
The preprotein translocase of the mitochondrial outer membrane (TOM) complex requires import receptors, an import channel, and small proteins, such as TOMM6, that regulate complex assembly (Kato and Mihara, 2008).
Using mass spectrometry to identify proteins within the HeLa cell TOM complex, Kato and Mihara (2008) identified TOMM6, which they called TOM6. The deduced 74-amino acid protein has a putative C-terminal transmembrane domain. Epitope-tagged TOM6 colocalized with the mitochondrial marker TIM17 (TIMM17A; 605057) in network structures in HeLa cells. Extraction and protease experiments confirmed that TOM6 associated with the TOM complex.
Using in vitro-synthesized small TOM proteins, Kato and Mihara (2008) found that TOM6 was assembled into an approximately 440-kD complex that included the mitochondrial import channel TOM40 (608061). RNA interference-mediated knockdown of TOM40 significantly reduced the levels of all small TOM proteins, including TOM5 (TOMM5; 616169), TOM6, and TOM7 (TOMM7; 607980). Knockdown of TOM5 or TOM6 had only modest effects on TOM complex stability, whereas knockdown of TOM7 significantly reduced TOM complex stability. Knockdown of the small TOM proteins had only minor effects on protein import and mitochondrial morphology.
Harbauer et al. (2014) found that CDK1 (116940) stimulated assembly of the main mitochondrial entry gate, the translocase of the outer membrane (TOM), in mitosis. In an S. cerevisiae assay, Harbauer et al. (2014) found that the molecular mechanism involves phosphorylation of the cytosolic precursor of TOM6 by cyclin CLB3-activated CDK1, leading to enhanced import of TOM6 into mitochondria. TOM6 phosphorylation promoted assembly of the protein import channel TOM40 and import of fusion proteins, thus stimulating the respiratory activity of mitochondria in mitosis. Harbauer et al. (2014) concluded that TOM6 phosphorylation provides a direct means for regulating mitochondrial biogenesis and activity in a cell cycle-specific manner.
Hartz (2015) mapped the TOMM6 gene to chromosome 6p21.1 based on an alignment of the TOMM6 sequence (GenBank AB435319) with the genomic sequence (GRCh38).
Harbauer, A. B., Opalinska, M., Gerbeth, C., Herman, J. S., Rao, S., Schonfisch, B., Guiard, B., Schmidt, O., Pfanner, N., Meisinger, C. Cell cycle-dependent regulation of mitochondrial preprotein translocase. Science 346: 1109-1113, 2014. [PubMed: 25378463] [Full Text: https://doi.org/10.1126/science.1261253]
Hartz, P. A. Personal Communication. Baltimore, Md. 1/6/2015.
Kato, H., Mihara, K. Identification of Tom5 and Tom6 in the preprotein translocase complex of human mitochondrial outer membrane. Biochem. Biophys. Res. Commun. 369: 958-963, 2008. [PubMed: 18331822] [Full Text: https://doi.org/10.1016/j.bbrc.2008.02.150]