This is a family of small, approximately 100 amino acid, proteins found from yeasts to humans. The majority of endogenous reactive oxygen species (ROS) in cells are produced by the mitochondrial respiratory chain. An increase or imbalance in ROS alters the intracellular redox homeostasis, triggers DNA damage, and may contribute to cancer development and progression (PMID:16842742). Members of this family are mitochondrial reactive oxygen species modulator 1 (Romo1) proteins that are responsible for increasing the level of ROS in cells. Increased Romo1 expression can have a number of other effects including: inducing premature senescence of cultured human fibroblasts (PMID:18313394, 18836179) and increased resistance to 5-fluorouracil (PMID:17537404).
This entry includes a group of mitochondrial proteins, including reactive oxygen species modulator 1 (Romo1) from animals and Mgr2 from fungi.
Budding yeast Mgr2 is a subunit of the TIM23 translocase complex, which translocates preproteins into and across the membrane and associates with the matrix-localized import motor. It is required for binding of Tim21 to TIM23(CORE). Mrg2 is essential for cell growth at elevated temperature and for efficient protein import [ (PUBMED:22613836) ].
Romo1 is responsible for increasing the level of ROS in cells. In various cancer cell lines with elevated levels of ROS there is also an increased abundance of Romo1 [ (PUBMED:16842742) ]. Increased Romo1 expression can have a number of other affects including: inducing premature senescence of cultured human fibroblasts [ (PUBMED:18836179) (PUBMED:18313394) ] and increased resistance to 5-fluorouracil [ (PUBMED:17537404) ].
Family alignment:
There are 1136 Romo1 domains in 1135 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing Romo1 domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with Romo1 domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing Romo1 domain in the selected taxonomic class.
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
Replicative senescence induced by Romo1-derived reactive oxygen species.
J Biol Chem. 2008; 283: 33763-71
Display abstract
Persistent accumulation of DNA damage induced by reactive oxygen species (ROS) isproposed to be a major contributor toward the aging process. Furthermore, anincrease in age-associated ROS is strongly correlated with aging in variousspecies, including humans. Here we showed that the enforced expression of the ROSmodulator 1 (Romo1) triggered premature senescence by ROS production, and thisalso contributed toward induction of DNA damage. Romo1-derived ROS was found tooriginate in the mitochondrial electron transport chain. Romo1 expressiongradually increased in proportion to population doublings of IMR-90 humanfibroblasts. An increase in ROS production in these cells with high populationdoubling was blocked by the Romo1 knockdown using Romo1 small interfering RNA.Romo1 knockdown also inhibited the progression of replicative senescence. Basedon these results, we suggest that age-related ROS levels increase, and thiscontributes to replicative senescence, which is directly associated with Romo1expression.
A critical role for Romo1-derived ROS in cell proliferation.
Biochem Biophys Res Commun. 2008; 369: 672-8
Display abstract
Low levels of endogenous reactive oxygen species (ROS) originating from NADPHoxidase have been implicated in various signaling pathways induced by growthfactors and mediated by cytokines. However, the main source of ROS is known to bethe mitochondria, and increased levels of ROS from the mitochondria have beenobserved in many cancer cells. Thus far, the mechanism of ROS production incancer cell proliferation in the mitochondria is not well-understood. We recentlyidentified a novel protein, ROS modulator 1 (Romo1), and reported that increased expression of Romo1-triggered ROS production in the mitochondria. The experimentsconducted in the present study showed that Romo1-derived ROS were indispensablefor the proliferation of both normal and cancer cells. Furthermore, whilst cellgrowth was inhibited by blocking the ERK pathway in cells transfected with siRNA directed against Romo1, the cell growth was recovered by addition of exogenoushydrogen peroxide. The results of this study suggest that Romo1-induced ROS mayplay an important role in redox signaling in cancer cells.
Drug resistance to 5-FU linked to reactive oxygen species modulator 1.
Biochem Biophys Res Commun. 2007; 359: 304-10
Display abstract
While acute oxidative stress triggers cell apoptosis or necrosis, persistentoxidative stress induces genomic instability and has been implicated in tumorprogression and drug resistance. In a previous report, we demonstrated thatreactive oxygen species modulator 1 (Romo1) expression was up-regulated in mostcancer cell lines and suggested that increased Romo1 expression might conferchronic oxidative stress to tumor cells. In this study, we show that enforcedRomo1 expression induces reactive oxygen species (ROS) production in themitochondria leading to massive cell death. However, tumor cells that adapt tooxidative stress by increasing manganese superoxide dismutase (MnSOD), Prx I, andBcl-2 showed drug resistance to 5-FU. To elucidate the relationship between5-FU-induced ROS production and Romo1 expression, Romo1 siRNA was used to inhibit5-FU-triggered Romo1 induction. Romo1 siRNA treatment efficiently blocked5-FU-induced ROS generation, demonstrating that 5-FU treatment stimulated ROSproduction through Romo1 induction. Based on these results we suggest thatcellular adaptive response to Romo1-induced ROS is another mechanism of drugresistance to 5-FU and Romo1 expression may provide a new clinical implication indrug resistance of cancer chemotherapy.
A novel protein, Romo1, induces ROS production in the mitochondria.
Biochem Biophys Res Commun. 2006; 347: 649-55
Display abstract
The majority of endogenous reactive oxygen species (ROS) are produced in themitochondrial respiratory chain. An imbalance in ROS production alters theintracellular redox homeostasis, triggers DNA damage, and contributes to cancerdevelopment and progression. This study identified a novel protein, reactiveoxygen species modulator 1 (Romo1), which is localized in the mitochondria. Romo1was found to increase the level of ROS in the cells. Increased Romo1 expressionwas observed in various cancer cell lines. This suggests that the increased Romo1expression during cancer progression may cause persistent oxidative stress totumor cells, which can increase their malignancy.
Links (links to other resources describing this domain)
