1.A.111. The Reactive Oxygen Species Modulator 1 (Romo1) Family
Zhao et al. 2009 identified a human nuclear gene (named MTGM or ROMO1) that encodes a small (79 aa) integral 2 TMS mitochondrial inner-membrane protein that shows high expression in both human brain tumor cell lines and tumor tissues. The gene is evolutionarily highly conserved, and its orthologs are 100% identical at the amino acid level in all analyzed mammalian species. The gene product is characterized by an unusual tetrad of the GxxxG motif in the transmembrane segment. Overexpression of the MTGM (mitochondrial targeting GxxxG motif) protein results in mitochondrial fragmentation and release of mitochondrial Smac/Diablo to the cytosol with no effect on apoptosis. MTGM-induced mitochondrial fission can be blocked by a dominant negative Drp1 mutant (Drp1-K38A). Overexpression of MTGM also results in inhibition of cell proliferation, stalling of cells in S phase and nuclear accumulation of gamma-H2AX. Knockdown of MTGM by RNA interference induces mitochondrial elongation, an increase of cell proliferation and inhibition of cell death induced by apoptotic stimuli. In conclusion, MTGM is an integral mitochondrial inner-membrane protein that coordinately regulates mitochondrial morphology and cell proliferation (Zhao et al. 2009).
Romo1 is known to regulate mitochondrial ROS production and to act as an essential redox sensor in mitochondrial dynamics. Lee et al. 2018 reported that Romo1 is a mitochondrial ion channel that differs from other identified ion channels. Romo1 is highly conserved with structural features of class II viroporins (virus-encoded nonselective cation channels). Indeed, Romo1 forms a nonselective cation channel with its amphipathic helical transmembrane domain necessary for pore-forming activity. Channel activity was specifically inhibited by Fe2+ ions, an essential transition metal ion in ROS metabolism. Using structural bioinformatics, Lee et al. 2018 designed an experimental data-guided structural model of Romo1 with a rational hexameric structure. They proposed that Romo1 establishes a new category of viroporin-like nonselective cation channels in eukaryotes. A peptide derived from the TMS of Romo1 Is a promising candidate for sepsis treatment and multidrug-resistant bacteria (You et al. 2021).
The MTGM protein of 79 aas and 2 TMSs, a member of the Romo1 family (Zhao et al. 2009).
MTGM of Homo sapiens
MRTM homologue of 108 aas and 2 TMSs.
MTGM of Aspergillus niger
MTGM homologue of 113 aas and 2 TMSs.
MTGM homologue of Saccharomyces cerevisiae
MTGM homologue of 74 aas
MTGM of Glycine max
Reactive oxygen species modulator 1 homologue, Romo1 family member of 128 aas.
Romo1 of Dictyostelium discoideum
MTGM protein of 80 aas.
MTGM of Galdieria sulfuraria
MTGM homologue of 149 aas
MTGM homologue of Tetrahymena thermophius
Uncharacterized protein of 165 aas and 2 TMSs.
UP of Theileria annulata
Uucharacterized putative reactive oxygen species modulator 1 protein of 168 aas and 2 C-terminal TMSs.
UP of Plasmodium falciparum