Single nucleotide polymorphisms linked to mitochondrial uncoupling protein genes UCP2 and UCP3 affect mitochondrial metabolism and healthy aging in female nonagenarians

Biogerontology

Volumn 17, Issue 4, 2016, Pages 725-736

  Kim, Sangkyu ^a   Myers, Leann ^b   Ravussin, Eric ^c   Cherry, Katie E ^d   Jazwinski, S Michal ^a  

^a TULANE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b TULANE UNIVERSITY   (United States)

^c PENNINGTON BIOMEDICAL RESEARCH CENTER   (United States)

^d LOUISIANA STATE UNIVERSITY   (United States)

Author keywords

Energy metabolism; Frailty; Healthy aging; Mitochondrial uncoupling; Single nucleotide polymorphism

Indexed keywords

REACTIVE OXYGEN METABOLITE; UNCOUPLING PROTEIN 2; UNCOUPLING PROTEIN 3; UCP2 PROTEIN, HUMAN;

3' UNTRANSLATED REGION; AGED; AGING; ARTICLE; BINDING SITE; BIOENERGY; BODY WEIGHT; CONTROLLED STUDY; ENERGY CONSUMPTION; ENERGY METABOLISM; FAT FREE MASS; FEMALE; GENE FREQUENCY; GENE INTERACTION; GENETIC ASSOCIATION; GENETIC RISK; HUMAN; MALE; MITOCHONDRIAL RESPIRATION; PHYSICAL ACTIVITY; PRIORITY JOURNAL; PROMOTER REGION; RESTING METABOLIC RATE; SEX DIFFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; TISSUE CULTURE CELL; UCP2 GENE; UCP3 GENE; VERY ELDERLY; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MITOCHONDRION; PHYSIOLOGY; SEXUAL DEVELOPMENT;

AGED, 80 AND OVER; AGING; ENERGY METABOLISM; FEMALE; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HUMANS; MITOCHONDRIA; POLYMORPHISM, SINGLE NUCLEOTIDE; SEX CHARACTERISTICS; UNCOUPLING PROTEIN 2; UNCOUPLING PROTEIN 3;

EID: 84960446048     PISSN: 13895729     EISSN: 15736768     Source Type: Journal    
DOI: 10.1007/s10522-016-9643-y     Document Type: Article

References (52)

1. Acosta A et al (2015) Association of UCP-3 rs1626521 with obesity and stomach functions in humans. Obes (Silver Spring) 23:898–906. doi:10.1002/oby.21039
2. Anand G, Shapiro DN, Dickman PS, Prochownik EV (1994) Rhabdomyosarcomas do not contain mutations in the DNA binding domains of myogenic transcription factors. J Clin Invest 93:5–9. doi:10.1172/jci116982
3. Andrews ZB, Horvath TL (2009) Uncoupling protein-2 regulates lifespan in mice. Am J Physiol Endocrinol Metab 296:E621–E627. doi:10.1152/ajpendo.90903.2008
4. Ayyasamy V et al (2011) Cellular model of Warburg effect identifies tumor promoting function of UCP2 in breast cancer and its suppression by genipin. PLoS One 6:e24792. doi:10.1371/journal.pone.0024792
5. Barrett JC (2009) Haploview: visualization and analysis of SNP genotype data. Cold Spring Harb Protoc 2009:pdb ip71. doi:10.1101/pdb.ip71
6. Battistelli C, Busanello A, Maione R (2014) Functional interplay between MyoD and CTCF in regulating long-range chromatin interactions during differentiation. J Cell Sci 127:3757–3767. doi:10.1242/jcs.149427
7. Boss O et al (1997) Uncoupling protein-3: a new member of the mitochondrial carrier family with tissue-specific expression. FEBS Lett 408:39–42
8. Bouchard C, Perusse L, Chagnon YC, Warden C, Ricquier D (1997) Linkage between markers in the vicinity of the uncoupling protein 2 gene and resting metabolic rate in humans. Hum Mol Genet 6:1887–1889
9. Boyle AP et al (2012) Annotation of functional variation in personal genomes using RegulomeDB. Genome Res 22:1790–1797. doi:10.1101/gr.137323.112
10. Brand MD et al (2004) Mitochondrial superoxide: production, biological effects, and activation of uncoupling proteins. Free Radic Biol Med 37:755–767. doi:10.1016/j.freeradbiomed.2004.05.034
11. Cao Y et al (2010) Genome-wide MyoD binding in skeletal muscle cells: a potential for broad cellular reprogramming. Dev Cell 18:662–674. doi:10.1016/j.devcel.2010.02.014
12. Crocco P, Montesanto A, Passarino G, Rose G (2011) A common polymorphism in the UCP3 promoter influences hand grip strength in elderly people. Biogerontology 12:265–271. doi:10.1007/s10522-011-9321-z
13. Dato S, Soerensen M, Montesanto A, Lagani V, Passarino G, Christensen K, Christiansen L (2012) UCP3 polymorphisms, hand grip performance and survival at old age: association analysis in two Danish middle aged and elderly cohorts. Mech Ageing Dev 133:530–537. doi:10.1016/j.mad.2012.06.004
14. Delgado-Olguin P, Brand-Arzamendi K, Scott IC, Jungblut B, Stainier DY, Bruneau BG, Recillas-Targa F (2011) CTCF promotes muscle differentiation by modulating the activity of myogenic regulatory factors. J Biol Chem 286:12483–12494. doi:10.1074/jbc.M110.164574
15. Dipietro L, Caspersen CJ, Ostfeld AM, Nadel ER (1993) A survey for assessing physical activity among older adults. Med Sci Sports Exerc 25:628–642
16. Echtay KS (2007) Mitochondrial uncoupling proteins–what is their physiological role? Free Radic Biol Med 43:1351–1371. doi:10.1016/j.freeradbiomed.2007.08.011
17. Echtay KS et al (2002) Superoxide activates mitochondrial uncoupling proteins. Nature 415:96–99. doi:10.1038/415096a
18. Filippova GN et al (1996) An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes. Mol Cell Biol 16:2802–2813
19. Frisard MI et al (2007) Aging, resting metabolic rate, and oxidative damage: results from the Louisiana Healthy Aging Study. J Gerontol A Biol Sci Med Sci 62:752–759
20. Gallagher IM, Jenner P, Glover V, Clow A (2000) CuZn-superoxide dismutase transgenic mice: no effect on longevity, locomotor activity and 3H-mazindol and 3H-spiperone binding over 19 months. Neurosci Lett 289:221–223
21. Gimeno RE et al (1997) Cloning and characterization of an uncoupling protein homolog: a potential molecular mediator of human thermogenesis. Diabetes 46:900–906
22. Ho PW et al (2012) Uncoupling protein-4 (UCP4) increases ATP supply by interacting with mitochondrial Complex II in neuroblastoma cells. PLoS One 7:e32810. doi:10.1371/journal.pone.0032810
23. Hsu YH, Niu T, Song Y, Tinker L, Kuller LH, Liu S (2008) Genetic variants in the UCP2-UCP3 gene cluster and risk of diabetes in the Women’s Health Initiative Observational Study. Diabetes 57:1101–1107. doi:10.2337/db07-1269
24. Hurtaud C, Gelly C, Chen Z, Levi-Meyrueis C, Bouillaud F (2007) Glutamine stimulates translation of uncoupling protein 2mRNA. Cell Mol Life Sci 64:1853–1860. doi:10.1007/s00018-007-7039-5
25. Jaburek M et al (1999) Transport function and regulation of mitochondrial uncoupling proteins 2 and 3. J Biol Chem 274:26003–26007
26. Jazwinski SM et al (2010) HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging. Aging Cell 9:698–708. doi:10.1111/j.1474-9726.2010.00600.x
27. Kim S, Jazwinski SM (2015) Quantitative measures of healthy aging and biological age. Healthy Aging Res. doi:10.12715/har.2015.4.26
28. Kim D, Jitrapakdee S, Thompson M (2007) Differential regulation of the promoter activity of the mouse UCP2 and UCP3 genes by MyoD and myogenin. J Biochem Mol Biol 40:921–927
29. Kim S, Welsh DA, Cherry KE, Myers L, Jazwinski SM (2013) Association of healthy aging with parental longevity. Age (Dordr) 35:1975–1982. doi:10.1007/s11357-012-9472-0
30. Kim S, Welsh DA, Ravussin E, Welsch MA, Cherry KE, Myers L, Jazwinski SM (2014) An elevation of resting metabolic rate with declining health in nonagenarians may be associated with decreased muscle mass and function in women and men, respectively. J Gerontol A Biol Sci Med Sci 69:650–656. doi:10.1093/gerona/glt150
31. Klaus S, Casteilla L, Bouillaud F, Ricquier D (1991) The uncoupling protein UCP: a membraneous mitochondrial ion carrier exclusively expressed in brown adipose tissue. Int J Biochem 23:791–801
32. Krauss S, Zhang CY, Lowell BB (2002) A significant portion of mitochondrial proton leak in intact thymocytes depends on expression of UCP2. Proc Natl Acad Sci USA 99:118–122. doi:10.1073/pnas.012410699
33. Krauss S, Zhang CY, Lowell BB (2005) The mitochondrial uncoupling-protein homologues. Nat Rev Mol Cell Biol 6:248–261. doi:10.1038/nrm1572
34. Kwok KH et al (2010) Mitochondrial UCP5 is neuroprotective by preserving mitochondrial membrane potential, ATP levels, and reducing oxidative stress in MPP+ and dopamine toxicity. Free Radic Biol Med 49:1023–1035. doi:10.1016/j.freeradbiomed.2010.06.017
35. Matthias A, Ohlson KBE, Fredriksson JM, Jacobsson A, Nedergaard J, Cannon B (2000) Thermogenic responses in brown fat cells are fully UCP1-dependent: UCP2 or UCP3 do not substitute for UCP1 in adrenergically or fatty acid-induced thermogenesis. J Biol Chem 275:25073–25081. doi:10.1074/jbc.M000547200
36. Mookerjee SA, Divakaruni AS, Jastroch M, Brand MD (2010) Mitochondrial uncoupling and lifespan. Mech Ageing Dev 131:463–472. doi:10.1016/j.mad.2010.03.010
37. Musa CV et al (2012) Four novel UCP3 gene variants associated with childhood obesity: effect on fatty acid oxidation and on prevention of triglyceride storage. Int J Obes (Lond) 36:207–217. doi:10.1038/ijo.2011.81
38. Pecqueur C et al (2001) Uncoupling protein 2, in vivo distribution, induction upon oxidative stress, and evidence for translational regulation. J Biol Chem 276:8705–8712. doi:10.1074/jbc.M006938200
39. Pecqueur C et al (2008) Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis-derived pyruvate utilization. Faseb J 22:9–18. doi:10.1096/fj.07-8945com
40. R_Core_Team (2014) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna
41. Rose G, Crocco P, De Rango F, Montesanto A, Passarino G (2011) Further support to the uncoupling-to-survive theory: the genetic variation of human UCP genes is associated with longevity. PLoS One 6:e29650. doi:10.1371/journal.pone.0029650
42. Rosenbloom KR et al (2015) The UCSC Genome Browser database: 2015 update. Nucleic Acids Res 43:D670–D681. doi:10.1093/nar/gku1177
43. Rousset S, Alves-Guerra MC, Mozo J, Miroux B, Cassard-Doulcier AM, Bouillaud F, Ricquier D (2004) The biology of mitochondrial uncoupling proteins. Diabetes 53(Suppl 1):S130–S135
44. Ruggiero C, Ferrucci L (2006) The endeavor of high maintenance homeostasis: resting metabolic rate and the legacy of longevity. J Gerontol A Biol Sci Med Sci 61:466–471
45. Schrauwen P, Xia J, Walder K, Snitker S, Ravussin E (1999) A novel polymorphism in the proximal UCP3 promoter region: effect on skeletal muscle UCP3 mRNA expression and obesity in male non-diabetic Pima Indians. Int J Obes Relat Metab Disord 23:1242–1245
46. Schrauwen P, Hesselink MK, Blaak EE, Borghouts LB, Schaart G, Saris WH, Keizer HA (2001) Uncoupling protein 3 content is decreased in skeletal muscle of patients with type 2 diabetes. Diabetes 50:2870–2873
47. Thomas SA, Palmiter RD (1997) Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline. Nature 387:94–97
48. Velloso LA, Degasperi GR, Vercesi AE, Saad MA (2009) Methods for assessing and modulating UCP2 expression and function. Methods Enzymol 457:395–404. doi:10.1016/s0076-6879(09)05022-8
49. Vozza A et al (2014) UCP2 transports C4 metabolites out of mitochondria, regulating glucose and glutamine oxidation. Proc Natl Acad Sci USA 111:960–965. doi:10.1073/pnas.1317400111
50. Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270
51. Zhang CY et al (2001) Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 105:745–755
52. Zhang Y et al (2009) Mice deficient in both Mn superoxide dismutase and glutathione peroxidase-1 have increased oxidative damage and a greater incidence of pathology but no reduction in longevity. J Gerontol A Biol Sci Med Sci 64:1212–1220. doi:10.1093/gerona/glp132