Gene Symbol: MED12
Description: mediator complex subunit 12
Alias: ARC240, CAGH45, FGS1, HOPA, MED12S, OHDOX, OKS, OPA1, TNRC11, TRAP230, mediator of RNA polymerase II transcription subunit 12, CAG repeat protein 45, OPA-containing protein, activator-recruited cofactor 240 kDa component, human opposite paired, mediator of RNA polymerase II transcription, subunit 12 homolog, thyroid hormone receptor-associated protein complex 230 kDa component, thyroid hormone receptor-associated protein, 230 kDa subunit, trinucleotide repeat containing 11 (THR-associated protein, 230 kDa subunit), trinucleotide repeat-containing gene 11 protein
Species: human
Products:     MED12

Top Publications

  1. Kim S, Xu X, Hecht A, Boyer T. Mediator is a transducer of Wnt/beta-catenin signaling. J Biol Chem. 2006;281:14066-75 pubmed
    ..Here, we show that beta-catenin physically and functionally targets the MED12 subunit in Mediator to activate transcription...
  2. Schwartz C, Tarpey P, Lubs H, Verloes A, May M, Risheg H, et al. The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene. J Med Genet. 2007;44:472-7 pubmed
    A novel missense mutation in the mediator of RNA polymerase II transcription subunit 12 (MED12) gene has been found in the original family with Lujan syndrome and in a second family (K9359) that was initially considered to have Opitz-..
  3. Donner A, Ebmeier C, Taatjes D, Espinosa J. CDK8 is a positive regulator of transcriptional elongation within the serum response network. Nat Struct Mol Biol. 2010;17:194-201 pubmed publisher
    ..Furthermore, CDK8-Mediator specifically interacts with positive transcription elongation factor b. Thus, we have uncovered a role for CDK8 in transcriptional regulation that may contribute to its oncogenic effects. ..
  4. Markowski D, Bartnitzke S, Löning T, Drieschner N, Helmke B, Bullerdiek J. MED12 mutations in uterine fibroids--their relationship to cytogenetic subgroups. Int J Cancer. 2012;131:1528-36 pubmed publisher
    ..Recently, mutations of the gene mediator subcomplex 12 (MED12) have been detected in a majority of fibroids but no information is available whether or not they co-occur with ..
  5. Lim W, Ong C, Tan J, Thike A, Ng C, Rajasegaran V, et al. Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma. Nat Genet. 2014;46:877-80 pubmed publisher
    ..sequencing of eight fibroadenomas with matching whole-blood samples revealed recurrent somatic mutations solely in MED12, which encodes a Mediator complex subunit...
  6. Mäkinen N, Mehine M, Tolvanen J, Kaasinen E, Li Y, Lehtonen H, et al. MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science. 2011;334:252-5 pubmed publisher
    ..different patients by exome sequencing and identified tumor-specific mutations in the mediator complex subunit 12 (MED12) gene in 10...
  7. Kämpjärvi K, Mäkinen N, Kilpivaara O, Arola J, Heinonen H, Bohm J, et al. Somatic MED12 mutations in uterine leiomyosarcoma and colorectal cancer. Br J Cancer. 2012;107:1761-5 pubmed publisher
    ..through exome sequencing that as many as 70% of uterine leiomyomas harbour specific mutations in exon 2 of mediator complex subunit 12 (MED12). In this work, we examined the role of MED12 exon 2 mutations in other tumour types.
  8. Ravegnini G, Mariño Enríquez A, Slater J, Eilers G, Wang Y, Zhu M, et al. MED12 mutations in leiomyosarcoma and extrauterine leiomyoma. Mod Pathol. 2013;26:743-9 pubmed publisher
    ..b>MED12, the mediator complex subunit 12 gene, has been recently implicated as an oncogene in as many as 70% of sporadic ..
  9. Bertsch E, Qiang W, Zhang Q, Espona Fiedler M, Druschitz S, Liu Y, et al. MED12 and HMGA2 mutations: two independent genetic events in uterine leiomyoma and leiomyosarcoma. Mod Pathol. 2014;27:1144-53 pubmed publisher
    Recent identification of somatic MED12 mutations in most uterine leiomyomas brings a new venue for the study of the tumorigenesis of leiomyomas...

More Information

Publications108 found, 100 shown here

  1. Kämpjärvi K, Park M, Mehine M, Kim N, Clark A, Bützow R, et al. Mutations in Exon 1 highlight the role of MED12 in uterine leiomyomas. Hum Mutat. 2014;35:1136-41 pubmed publisher
    ..We recently discovered by exome sequencing that specific exon 2 mutations in mediator complex subunit 12 (MED12) are extremely common in uterine leiomyomas...
  2. Risheg H, Graham J, Clark R, Rogers R, Opitz J, Moeschler J, et al. A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome. Nat Genet. 2007;39:451-3 pubmed named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex.
  3. Mäkinen N, Heinonen H, Moore S, Tomlinson I, van der Spuy Z, Aaltonen L. MED12 exon 2 mutations are common in uterine leiomyomas from South African patients. Oncotarget. 2011;2:966-9 pubmed
    ..Recently, we demonstrated that exon 2 of the MED12 gene is somatically altered in up to 70 per cent of uterine leiomyomas in a series of Finnish (Caucasian) patients...
  4. Markowski D, Huhle S, Nimzyk R, Stenman G, Löning T, Bullerdiek J. MED12 mutations occurring in benign and malignant mammalian smooth muscle tumors. Genes Chromosomes Cancer. 2013;52:297-304 pubmed publisher
    Mutations of the mediator subcomplex 12 gene (MED12) recently have been described in a large group of uterine leiomyomas (UL) but only in a single malignant uterine smooth muscle tumor...
  5. Matsubara A, Sekine S, Yoshida M, Yoshida A, Taniguchi H, Kushima R, et al. Prevalence of MED12 mutations in uterine and extrauterine smooth muscle tumours. Histopathology. 2013;62:657-61 pubmed publisher
    To determine the prevalence of MED12 mutations in smooth muscle tumours of different organs...
  6. Taatjes D, Naar A, Andel F, Nogales E, Tjian R. Structure, function, and activator-induced conformations of the CRSP coactivator. Science. 2002;295:1058-62 pubmed
    ..These results suggest that CRSP may potentiate transcription via specific activator-induced conformational changes. ..
  7. Turunen M, Spaeth J, Keskitalo S, Park M, Kivioja T, Clark A, et al. Uterine leiomyoma-linked MED12 mutations disrupt mediator-associated CDK activity. Cell Rep. 2014;7:654-60 pubmed publisher
    Somatic mutations in exon 2 of the RNA polymerase II transcriptional Mediator subunit MED12 occur at very high frequency (?70%) in uterine leiomyomas...
  8. McGuire M, Yatsenko A, Hoffner L, Jones M, Surti U, Rajkovic A. Whole exome sequencing in a random sample of North American women with leiomyomas identifies MED12 mutations in majority of uterine leiomyomas. PLoS ONE. 2012;7:e33251 pubmed publisher
    ..Whole exome sequencing revealed that the gene encoding transcription factor MED12 (Mediator complex subunit 12) harbored heterozygous missense mutations caused by single nucleotide variants in ..
  9. Pérot G, Croce S, Ribeiro A, Lagarde P, Velasco V, Neuville A, et al. MED12 alterations in both human benign and malignant uterine soft tissue tumors. PLoS ONE. 2012;7:e40015 pubmed publisher
    ..The idea that a leiomyosarcoma could derive from a leiomyoma is still controversial. Recently MED12 mutations have been reported in uterine leiomyomas...
  10. Meyer K, Donner A, Knuesel M, York A, Espinosa J, Taatjes D. Cooperative activity of cdk8 and GCN5L within Mediator directs tandem phosphoacetylation of histone H3. EMBO J. 2008;27:1447-57 pubmed publisher
    ..Indeed our results suggest that T/G-Mediator directs early events-such as modification of chromatin templates-in transcriptional activation. ..
  11. Ding N, Zhou H, Esteve P, Chin H, Kim S, Xu X, et al. Mediator links epigenetic silencing of neuronal gene expression with x-linked mental retardation. Mol Cell. 2008;31:347-59 pubmed publisher
    ..We show that the MED12 interface in Mediator links REST with G9a-dependent histone H3K9 dimethylation to suppress neuronal genes in ..
  12. Knuesel M, Meyer K, Donner A, Espinosa J, Taatjes D. The human CDK8 subcomplex is a histone kinase that requires Med12 for activity and can function independently of mediator. Mol Cell Biol. 2009;29:650-61 pubmed publisher
    The four proteins CDK8, cyclin C, Med12, and Med13 can associate with Mediator and are presumed to form a stable "CDK8 subcomplex" in cells...
  13. Je E, Kim M, Min K, Yoo N, Lee S. Mutational analysis of MED12 exon 2 in uterine leiomyoma and other common tumors. Int J Cancer. 2012;131:E1044-7 pubmed publisher
    Recurrent somatic mutations in MED12 exon 2 have recently been reported in uterine leiomyomas. The recurrent nature of the mutations strongly suggests that the mutations may play important roles in the pathogenesis of uterine leiomyomas...
  14. Reddy P, Yin X, Manczak M, Kumar S, Pradeepkiran J, Vijayan M, et al. Mutant APP and amyloid beta-induced defective autophagy, mitophagy, mitochondrial structural and functional changes and synaptic damage in hippocampal neurons from Alzheimer's disease. Hum Mol Genet. 2018;27:2502-2516 pubmed publisher
    ..mRNA and protein levels of mitochondrial fission genes, Drp1 and Fis1 and decreased levels fusion (Mfn1, Mfn2 and Opa1) biogenesis (PGC1α, NRF1, NRF2 & TFAM), autophagy (ATG5 & LC3BI, LC3BII), mitophagy (PINK1 & TERT, ..
  15. Conca Dioguardi C, Uslu B, Haynes M, Kurus M, Gul M, Miao D, et al. Granulosa cell and oocyte mitochondrial abnormalities in a mouse model of fragile X primary ovarian insufficiency. Mol Hum Reprod. 2016;22:384-96 pubmed publisher
    ..Finally, aberrant mitochondrial gene expression was detected. Mitofusin 2 (Mfn2) and Optic atrophy 1 (Opa1), genes involved in mitochondrial fusion and structure, respectively, were significantly decreased in whole ovaries ..
  16. de Oliveira Souza A, Couto Lima C, Rosa Machado M, Espreafico E, Pinheiro Ramos R, Alberici L. Protective action of Omega-3 on paraquat intoxication in Drosophila melanogaster. J Toxicol Environ Health A. 2017;80:1050-1063 pubmed publisher
    ..dynamin-related protein (DRP1), mitochondrial assembly regulatory factor (MARF), mitochondrial dynamin like GTPase (OPA1), and peroxisome proliferator-activated receptor-? coactivator 1? (PGC1?)...
  17. Li S, Zhao H, Wang Y, Shao Y, Liu J, Xing M. Arsenic-induced cardiotoxicity correlates with mitochondrial damage and trace elements imbalance in broiler chickens. Poult Sci. 2019;98:734-744 pubmed publisher
    ..cell lymphoma/leukemia 2 (Bcl2) were significantly decreased and dynamin-related protein 1 (Drp1), Optic atrophy 1 (Opa1), mitochondrial fission factor 1 (Mfn1), Mfn2, p53, caspase-8, Bcl-2 associated X protein (Bax), caspase-3, caspase-..
  18. Li F, Lang F, Wang Y, Zhai C, Zhang C, Zhang L, et al. Cyanidin ameliorates endotoxin-induced myocardial toxicity by modulating inflammation and oxidative stress through mitochondria and other factors. Food Chem Toxicol. 2018;120:104-111 pubmed publisher
    ..induced mediated myocardial injury was the modulation of mitochondria, its oxidative damage and associated factor Opa1 and Trx1...
  19. Knowlton W, Hubert T, Wu Z, Chisholm A, Jin Y. A Select Subset of Electron Transport Chain Genes Associated with Optic Atrophy Link Mitochondria to Axon Regeneration in Caenorhabditis elegans. Front Neurosci. 2017;11:263 pubmed publisher
    ..uptake, mitophagy, or fission and fusion were largely dispensable for axon regrowth, with the exception of eat-3/Opa1...
  20. Huang S, Huang C, Sheen J, Lin T, Liao P, Huang W, et al. Phyllanthus urinaria's Inhibition of Human Osteosarcoma Xenografts Growth in Mice is Associated with Modulation of Mitochondrial Fission/Fusion Machinery. Am J Chin Med. 2016;44:1507-1523 pubmed
    ..decrease in the mitochondrial fusion proteins, including mitofusin 1/2 (Mfn1/2) and optic atrophy type 1 (Opa1), as well as an increase in the fission protein dynamin-related protein 1 (Drp1)...
  21. Huang T, Santarelli R, Starr A. Mutation of OPA1 gene causes deafness by affecting function of auditory nerve terminals. Brain Res. 2009;1300:97-104 pubmed publisher
    ..We sequenced OPA1 gene and recorded cochlear receptor and neural potentials before cochlear implantation...
  22. Long A, Owens K, Schlappal A, Kristian T, Fishman P, Schuh R. Effect of nicotinamide mononucleotide on brain mitochondrial respiratory deficits in an Alzheimer's disease-relevant murine model. BMC Neurol. 2015;15:19 pubmed publisher
    ..mutant APP, NAD(+)-dependent substrates (SIRT1 and CD38) in homogenates and fission/fusion proteins (DRP1, OPA1 and MFN2) in mitochondria isolated from brain...
  23. Chang A, Kang Y, Doering T. Cdk8 and Ssn801 Regulate Oxidative Stress Resistance and Virulence in Cryptococcus neoformans. MBio. 2019;10: pubmed publisher
    ..focused on the Kinase Module of Mediator, which consists of cyclin C (Ssn801), cyclin-dependent kinase 8 (Cdk8), Med12, and Med13. This module provides important inhibitory control of Mediator complex assembly and activity...
  24. Rubenstein M, Hollowell C, Guinan P. Suppression of BCL2 by Antisense Oligonucleotides and Compensation by Non-Targeted Genes May Enhance Tumor Proliferation. In Vivo. 2015;29:687-93 pubmed
    ..of the androgen receptor (AR), its p300 and interleukin-6 (IL6) co-activators, polymerase transcription mediator (MED12), and growth-regulating signal transducer (STAT3)...
  25. Boucret L, Chao de la Barca J, Morinière C, Desquiret V, Ferré L Hôtellier V, Descamps P, et al. Relationship between diminished ovarian reserve and mitochondrial biogenesis in cumulus cells. Hum Reprod. 2015;30:1653-64 pubmed publisher
    ..13), optic atrophy 1 (OPA1) (VIP = 1.89) and the transcription factor associated with mitochondria (TFAM) (VIP = 1.32)...
  26. Briffa J, Grinfeld E, McAinch A, Poronnik P, Hryciw D. Short term exposure to elevated levels of leptin reduces proximal tubule cell metabolic activity. Mol Cell Endocrinol. 2014;382:38-45 pubmed publisher
    ..However, p44/42 and mTOR play no role the reduced protein content per cell in OKs exposed to leptin. Therefore, leptin modulates metabolic activity in PTCs via an mTOR regulated pathway.
  27. Di Tommaso S, Massari S, Malvasi A, Vergara D, Maffia M, Greco M, et al. Selective genetic analysis of myoma pseudocapsule and potential biological impact on uterine fibroid medical therapy. Expert Opin Ther Targets. 2015;19:7-12 pubmed publisher
    Mutations in Mediator Complex Subunit 12 (MED12) gene are typical genomic aberrations, commonly detected in a high percentage of uterine leiomyomas (ULs)...
  28. Greene N, Lee D, Brown J, Rosa M, Brown L, Perry R, et al. Mitochondrial quality control, promoted by PGC-1α, is dysregulated by Western diet-induced obesity and partially restored by moderate physical activity in mice. Physiol Rep. 2015;3: pubmed publisher
    ..Mitochondrial fusion seems diminished (reduced MFN2, Opa1 proteins), with no significant changes in fission, suggesting a shift in balance of dynamics regulation favoring ..
  29. Maempel J, Clement N, Brenkel I, Walmsley P. Range of movement correlates with the Oxford knee score after total knee replacement: A prediction model and validation. Knee. 2016;23:511-6 pubmed publisher
    ..The aim of this study was to assess the relationship between the Oxford knee score (OKS) and range of motion (ROM) after TKR, and to construct and validate prediction models of ROM from the measured OKS...
  30. van Egmond N, Stolwijk N, van Heerwaarden R, van Kampen A, Keijsers N. Gait analysis before and after corrective osteotomy in patients with knee osteoarthritis and a valgus deformity. Knee Surg Sports Traumatol Arthrosc. 2017;25:2904-2913 pubmed publisher
    ..A significant improvement was found in WOMAC [80.8 (SD 16.1), p = 0.000], KOS [74.9 (SD 14.7), p = 0.018], OKS [21.2 (SD 7.5), p = 0.000] and VAS-pain [32.9 (SD 20.9), p = 0...
  31. Papadopoulou T, Kaymak A, Sayols S, Richly H. Dual role of Med12 in PRC1-dependent gene repression and ncRNA-mediated transcriptional activation. Cell Cycle. 2016;15:1479-93 pubmed publisher
    ..One means of controlling the function of Mediator is provided by the binding of the Cdk8 module (Med12, Cdk8, Ccnc and Med13) to the core Mediator...
  32. Yeh J, Chen J, Lim J, Pang H, Tay D, Chia S, et al. Postoperative fixed flexion deformity greater than 10° lead to poorer functional outcome 10 years after unicompartmental knee arthroplasty. Knee Surg Sports Traumatol Arthrosc. 2018;26:1723-1727 pubmed publisher
    ..was quantified using Knee Society Function Score (KSFS), Knee Society Knee Score (KSKS) and Oxford Knee Score (OKS). At 10 years after UKA, the mean KSKS and OKS were 6?±?5 (95% CI 6-18, p?=?0.050) and 5?±?2 (95% CI 0-9, p?=?0...
  33. Kuuluvainen E, Domènech Moreno E, Niemelä E, Makela T. Depletion of Mediator Kinase Module Subunits Represses Superenhancer-Associated Genes in Colon Cancer Cells. Mol Cell Biol. 2018;38: pubmed publisher
    ..Superenhancers are enriched for BRD4 and Mediator, and both BRD4 and the Mediator MED12 subunit are disproportionally required for expression of superenhancer-associated genes in stem cells...
  34. Consolato F, Maltecca F, Tulli S, Sambri I, Casari G. m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics. J Cell Sci. 2018;131: pubmed publisher
    The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (i)-AAA protease complex] and OMA1, is a crucial step in the regulation of mitochondrial dynamics...
  35. Wang Q, Sharma D, Ren Y, Fondell J. A coregulatory role for the TRAP-mediator complex in androgen receptor-mediated gene expression. J Biol Chem. 2002;277:42852-8 pubmed
    ..Collectively, these data suggest that TRAP-Mediator may play an important coregulatory role in AR-mediated gene expression. ..
  36. Gwynne Jones D, Iosua E. Rationing of hip and knee replacement: effect on the severity of patient-reported symptoms and the demand for surgery in Otago. N Z Med J. 2016;129:59-66 pubmed
    ..Demographic details and preoperative patient reported outcome scores (Oxford hip or knee score (OHS,OKS) and a reduced Western Ontario and McMaster Osteoarthritis Index (WOMAC) score (RWS) were collected prospectively ..
  37. Chun B, Rizzo J. Dominant optic atrophy: updates on the pathophysiology and clinical manifestations of the optic atrophy 1 mutation. Curr Opin Ophthalmol. 2016;27:475-480 pubmed
    ..optic atrophy (DOA) to better understand the complexities of pathophysiology caused by the optic atrophy 1 (OPA1) mutation...
  38. Horbay R, Bilyy R. Mitochondrial dynamics during cell cycling. Apoptosis. 2016;21:1327-1335 pubmed
    ..Several proteins, such as Drp1, Fis1, Kif-family proteins, Opa1, Bax and mitofusins change in activity and might link the mitochondrial fission/fusion events with processes such ..
  39. Liu K, Frazier W. Phosphorylation of the BNIP3 C-Terminus Inhibits Mitochondrial Damage and Cell Death without Blocking Autophagy. PLoS ONE. 2015;10:e0129667 pubmed publisher
    ..of cell death upon C-terminal BNIP3 phosphorylation, can be explained by a diminished interaction between BNIP3 and OPA1, a key regulator of mitochondrial fusion and mitochondrial inner membrane structure...
  40. Jin X, Su R, Li R, Song L, Chen M, Cheng L, et al. Amelioration of particulate matter-induced oxidative damage by vitamin c and quercetin in human bronchial epithelial cells. Chemosphere. 2016;144:459-66 pubmed publisher
    ..oxygen species (ROS) generation, and inhibited mitochondrial genes expressions, including fusion proteins Mfn1 and OPA1, along with biogenesis markers SIRT1 and p53R2...
  41. Ryan Z, Craig T, Folmes C, Wang X, Lanza I, Schaible N, et al. 1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells. J Biol Chem. 2016;291:1514-28 pubmed publisher
    ..In 1α,25(OH)2D3-treated cells, mitochondrial volume and branching and expression of the pro-fusion protein OPA1 (optic atrophy 1) increased, whereas expression of the pro-fission proteins Fis1 (fission 1) and Drp1 (dynamin 1-..
  42. Bultman S, Holley D, G de Ridder G, Pizzo S, Sidorova T, Murray K, et al. BRG1 and BRM SWI/SNF ATPases redundantly maintain cardiomyocyte homeostasis by regulating cardiomyocyte mitophagy and mitochondrial dynamics in vivo. Cardiovasc Pathol. 2016;25:258-269 pubmed publisher
    ..mitochondria size, reduced numbers of mitochondria, and an altered expression of genes regulating fusion (Mfn1, Opa1) and fission (Drp1)...
  43. Young S, Walker M, Bayan A, Briant Evans T, Pavlou P, Farrington B. The Chitranjan S. Ranawat Award : No Difference in 2-year Functional Outcomes Using Kinematic versus Mechanical Alignment in TKA: A Randomized Controlled Clinical Trial. Clin Orthop Relat Res. 2017;475:9-20 pubmed publisher
    ..size at a minimum of 45 patients per treatment arm based on a 5-point improvement in the mean Oxford Knee Score (OKS; the previously reported minimum clinically significant difference for the OKS in TKA), a pooled SD of 8...
  44. Al Hendy A, Laknaur A, Diamond M, Ismail N, Boyer T, Halder S. Silencing Med12 Gene Reduces Proliferation of Human Leiomyoma Cells Mediated via Wnt/β-Catenin Signaling Pathway. Endocrinology. 2017;158:592-603 pubmed publisher
    ..In this work, the effect of silencing the mediator complex subunit 12 (Med12) gene in human uterine fibroid cells was evaluated...
  45. Liao C, Ashley N, Diot A, Morten K, Phadwal K, Williams A, et al. Dysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutations. Neurology. 2017;88:131-142 pubmed publisher
    To investigate mitophagy in 5 patients with severe dominantly inherited optic atrophy (DOA), caused by depletion of OPA1 (a protein that is essential for mitochondrial fusion), compared with healthy controls...
  46. Huang S, Huang C, Huang W, Lin T, Liao P, Wang P, et al. Tanshinone IIA induces intrinsic apoptosis in osteosarcoma cells both in vivo and in vitro associated with mitochondrial dysfunction. Sci Rep. 2017;7:40382 pubmed publisher
    ..Tan IIA administration resulted in a significant decrease in the mitochondrial fusion proteins, Mfn1/2 and Opa1, as well as an increase in the fission protein Drp1...
  47. Laforge M, Rodrigues V, Silvestre R, Gautier C, Weil R, Corti O, et al. NF-κB pathway controls mitochondrial dynamics. Cell Death Differ. 2016;23:89-98 pubmed publisher
    The Optic atrophy 1 protein (OPA1) is a key element in the dynamics and morphology of mitochondria...
  48. Anusree S, Nisha V, Priyanka A, Raghu K. Insulin resistance by TNF-α is associated with mitochondrial dysfunction in 3T3-L1 adipocytes and is ameliorated by punicic acid, a PPARγ agonist. Mol Cell Endocrinol. 2015;413:120-8 pubmed publisher
    ..found to ameliorate TNF-α induced alterations in proteins associated with mitochondrial dynamics like FIS1 and OPA1. These findings suggest that PA can be considered as an active lead for the management of insulin resistance and ..
  49. Baur J, Zwicky L, Hirschmann M, Ilchmann T, Clauss M. Metal backed fixed-bearing unicondylar knee arthroplasties using minimal invasive surgery: a promising outcome analysis of 132 cases. BMC Musculoskelet Disord. 2015;16:177 pubmed publisher
    ..Clinical outcome was assessed using the American knee society score (AKS) and the Oxford knee score (OKS)...
  50. Nolli C, Goffrini P, Lazzaretti M, Zanna C, Vitale R, Lodi T, et al. Validation of a MGM1/OPA1 chimeric gene for functional analysis in yeast of mutations associated with dominant optic atrophy. Mitochondrion. 2015;25:38-48 pubmed publisher
    Mutations in OPA1 are associated with DOA or DOA plus. Novel mutations in OPA1 are periodically identified, but often the causative effect of the mutation is not demonstrated...
  51. Sanchis Gomar F, Lippi G, Lucia A. 'Mitotherapy' for Heart Failure. Trends Mol Med. 2016;22:267-269 pubmed publisher
    ..Recent research highlights OPA1, a dynamin-like GTPase mediating mitochondrial fusion, as well as the 'mitoproteases' OMA1 and YME1L, as potential ..
  52. Xu H, Gao J, Wang F. Altered mitochondrial expression genes in patients receiving right ventricular apical pacing. Exp Mol Pathol. 2016;100:469-75 pubmed publisher
    ..The gene signature (OPA1, CTSA, NDUFA1, STK10 and PRDX1) was able to identify patients post-implant with an area under receiver operating ..
  53. Narayanan D, Phadke S. A novel variant in MED12 gene: Further delineation of phenotype. Am J Med Genet A. 2017;173:2257-2260 pubmed publisher
    b>MED12 is a multiprotein mediator complex, which has a role in cell growth and differentiation and has been implicated in three distinct X-linked intellectual disability syndromes with distinctive clinical features...
  54. Standley R, Distefano G, Pereira S, Tian M, Kelly O, Coen P, et al. Effects of ?-hydroxy-?-methylbutyrate on skeletal muscle mitochondrial content and dynamics, and lipids after 10 days of bed rest in older adults. J Appl Physiol (1985). 2017;123:1092-1100 pubmed publisher
    ..measured protein markers of mitochondrial content [oxidative phosphorylation (OXPHOS)], fusion and fission (MFN2, OPA1, FIS1, and DRP1), autophagy (Beclin1, LC3B, and BNIP3), and atrophy [poly-ubiquinated proteins (poly-ub)] by ..
  55. Beyer K, Klauck S, Benner A, Poustka F, Poustka A. Association studies of the HOPA dodecamer duplication variant in different subtypes of autism. Am J Med Genet. 2002;114:110-5 pubmed
    The HOPA gene in Xq13 is coding for a protein involved in a nuclear thyroid receptor complex...
  56. Ishihara T, Kohno H, Ishihara N. Physiological roles of mitochondrial fission in cultured cells and mouse development. Ann N Y Acad Sci. 2015;1350:77-81 pubmed publisher
    ..occur by repeated membrane fusion and fission events, which are regulated by three types of GTPase proteins: OPA1, Mfn1/2, Drp1 in mammalian cells...
  57. Thomas Claudepierre A, Robert I, Rocha P, Raviram R, Schiavo E, Heyer V, et al. Mediator facilitates transcriptional activation and dynamic long-range contacts at the IgH locus during class switch recombination. J Exp Med. 2016;213:303-12 pubmed publisher
    ..Nevertheless, little is known about the underlying mechanisms. In this study, we show that Med1 and Med12, two subunits of the mediator complex implicated in transcription initiation and long-range enhancer/promoter loop ..
  58. Alvand A, Khan T, Jenkins C, Rees J, Jackson W, Dodd C, et al. The impact of patient-specific instrumentation on unicompartmental knee arthroplasty: a prospective randomised controlled study. Knee Surg Sports Traumatol Arthrosc. 2018;26:1662-1670 pubmed publisher
    ..Functional outcome was determined using the Oxford Knee Score (OKS)...
  59. Kameoka S, Adachi Y, Okamoto K, Iijima M, Sesaki H. Phosphatidic Acid and Cardiolipin Coordinate Mitochondrial Dynamics. Trends Cell Biol. 2018;28:67-76 pubmed publisher
    ..These two lipids interact with the core components of mitochondrial fusion and division (Opa1, mitofusin, and Drp1) to activate and inhibit these dynamin-related GTPases...
  60. Xiang Y, Zhang D, Wang D, Li Y, Yao Y. Common variants of OPA1 conferring genetic susceptibility to leprosy in Han Chinese from Southwest China. J Dermatol Sci. 2015;80:133-41 pubmed publisher
    ..leprae. The optic atrophy 1 (OPA1) gene plays an essential role in mitochondria, which function in cellular energy supply and innate immunity...
  61. Nomura R, Sato T, Sato Y, Medin J, Kushimoto S, Yanagisawa T. Azidothymidine-triphosphate impairs mitochondrial dynamics by disrupting the quality control system. Redox Biol. 2017;13:407-417 pubmed publisher
    ..Drp)1 and the Drp1 receptor mitochondrial fission factor (Mff) was upregulated whereas that of optic atrophy 1 (Opa1) was downregulated following AZT treatment...
  62. Tutter A, Kowalski M, Baltus G, Iourgenko V, Labow M, Li E, et al. Role for Med12 in regulation of Nanog and Nanog target genes. J Biol Chem. 2009;284:3709-18 pubmed publisher
    ..b>Med12 is part of a subcomplex of four proteins associated with the core Mediator complex and has been found to function ..
  63. Xu X, Zhou H, Boyer T. Mediator is a transducer of amyloid-precursor-protein-dependent nuclear signalling. EMBO Rep. 2011;12:216-22 pubmed publisher
    ..In this study, we show that the AICD activates transcription by targeting MED12, an RNA polymerase II transcriptional Mediator subunit that is implicated in human cognitive development...
  64. Zhou H, Spaeth J, Kim N, Xu X, Friez M, Schwartz C, et al. MED12 mutations link intellectual disability syndromes with dysregulated GLI3-dependent Sonic Hedgehog signaling. Proc Natl Acad Sci U S A. 2012;109:19763-8 pubmed publisher
    Recurrent missense mutations in the RNA polymerase II Mediator subunit MED12 are associated with X-linked intellectual disability (XLID) and multiple congenital anomalies, including craniofacial, musculoskeletal, and behavioral defects ..
  65. Lesca G, Moizard M, Bussy G, Boggio D, Hu H, Haas S, et al. Clinical and neurocognitive characterization of a family with a novel MED12 gene frameshift mutation. Am J Med Genet A. 2013;161A:3063-71 pubmed publisher
    ..described as distinct syndromes with overlapping non-specific features and different missense mutations of the MED12 gene have been reported in all of them...
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    ..Provoked symptoms for Gaze-Stabilization (GST), Rapid Eye Horizontal (REH), Optokinetic Stimulation (OKS), Smooth-Pursuit Slow (SPS) and Fast (SPF) tests, total combined symptoms scores and near point convergence (NPC) ..
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    ..aberrations to next-generation sequencing-based approaches that led to the discovery of highly recurrent MED12 mutations...
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    ..b>MED12 [MIM *300188] (mediator complex subunit 12) mutations have been linked to numerous XLID syndromes, including Lujan,..
  69. Martin Fernandez J, García Maroto R, Sánchez Jiménez F, Bau González A, Valencia García H, Gutiérrez Teira B, et al. Validation of the Spanish version of the Oxford knee score and assessment of its utility to characterize quality of life of patients suffering from knee osteoarthritis: a multicentric study. Health Qual Life Outcomes. 2017;15:186 pubmed publisher
    Knee osteoarthritis (OA) represents a heavy burden for patients and the society as a whole. The Oxford Knee Score (OKS) is a well known tool to assess the quality of life in patients with Knee OA...
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    ..Risheg et al. [Risheg et al. (2007); Nat Genet 39:451-453] identified an identical mutation (p.R961W) in MED12 in six families with Opitz-Kaveggia syndrome, including a surviving affected man from the family reported in 1974...
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    Fibroadenomas (FAs) and phyllodes tumours (PTs) are fibroepithelial tumours. Mutations in MED12 exon 2 have been reported in FAs. This study investigated the MED12 mutations in a spectrum of fibroepithelial tumours...
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    ..Mutations in MED12 are linked with a broad spectrum of genetic disorders with X-linked intellectual disability that are difficult to ..
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    ..We used a large-scale RNAi screen to identify MED12, a component of the transcriptional MEDIATOR complex that is mutated in cancers, as a determinant of response to ..
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    ..Mutations in exon 2 of the gene encoding MED12, a key subunit of the regulatory kinase module in Mediator, are extremely frequent in uterine leiomyomas, breast ..
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    ..Breast fibroepithelial lesions, including PTs and fibroadenomas, are characterized by recurrent MED12 exon 2 somatic mutations...
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    ..and protein levels of Drp1 and Fis1 (fission) and CypD (matrix) genes, and increased levels of Mfn1, Mfn2 and Opa1 (fusion), Nrf1, Nrf2, PGC1?, TFAM (biogenesis) and synaptophysin, PSD95, synapsin 1, synaptobrevin 1, neurogranin, ..
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    ..enzymes (Sod1, Gpx1, Gpx4), activated genes regulating mitochondrial fission/fusion (Mfn1, Mfn2, Dnm1l, Opa1, Fis1), subunits of ETC complexes (mt-Nd1, Sdha, mt-Cytb) and modulated expression of several TFs, enhanced Foxo1 ..
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    ..cancer (PCa), Barbieri and colleagues using whole-exome sequencing identified a novel recurrently mutated gene, MED12, in 5.4% of primary PCa...
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    ..A large proportion of UL has mutations in MED12. Multiple and solitary ULs usually manifest with different severities, suggesting that their origin and growth ..
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    ..In this study, the frequency of MED12 mutations in 176 PTs (49 benign, 49 borderline, and 78 malignant) was determined and the prognostic effect of ..
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    ..The role of nuclear-receptor ligands may, in part, be to recruit such a cofactor complex to the receptor and, in doing so, to enhance transcription of target genes. ..
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    ..Notably, it is emphasized that cristae shape is governed by ATP-synthase dimers, MICOS complexes, OPA1 isoforms and the umbrella of their regulation, and also dependent on local protonmotive force (electrical potential ..
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    The mitochondrial contact site and cristae organizing system (MICOS) and Optic atrophy 1 (OPA1) control cristae shape, thus affecting mitochondrial function and apoptosis...
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    ..CCCP increased PGAM5, dynamin-related protein 1 (DRP1), and optic atrophy 1 (OPA1) expression of the mitochondrial fraction in a time-dependent manner...