Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Focus on Europe

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Originally published in Science Express on 21 October 2004
Science 12 November 2004:
Vol. 306. no. 5699, pp. 1190 - 1194
DOI: 10.1126/science.1102521
Prev | Table of Contents | Next

Reports

A Cluster of Metabolic Defects Caused by Mutation in a Mitochondrial tRNA

Frederick H. Wilson,1,2,3* Ali Hariri,1,4* Anita Farhi,1,2 Hongyu Zhao,2,5 Kitt Falk Petersen,4 Hakan R. Toka,1,2 Carol Nelson-Williams,1,2 Khalid M. Raja,8 Michael Kashgarian,6 Gerald I. Shulman,1,4,7 Steven J. Scheinman,8 Richard P. Lifton1,2,3,4{dagger}

Hypertension and dyslipidemia are risk factors for atherosclerosis and occur together more often than expected by chance. Although this clustering suggests shared causation, unifying factors remain unknown. We describe a large kindred with a syndrome including hypertension, hypercholesterolemia, and hypomagnesemia. Each phenotype is transmitted on the maternal lineage with a pattern indicating mitochondrial inheritance. Analysis of the mitochondrial genome of the maternal lineage identified a homoplasmic mutation substituting cytidine for uridine immediately 5' to the mitochondrial transfer RNAIle anticodon. Uridine at this position is nearly invariate among transfer RNAs because of its role in stabilizing the anticodon loop. Given the known loss of mitochondrial function with aging, these findings may have implications for the common clustering of these metabolic disorders.

1 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
2 Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
3 Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06510, USA.
4 Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
5 Department of Biostatistics, Yale University School of Medicine, New Haven, CT 06510, USA.
6 Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
7 Department of Cell and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA.
8 Department of Medicine, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.


* These authors contributed equally to this manuscript.

{dagger} To whom correspondence should be addressed. E-mail: richard.lifton{at}yale.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Transient receptor potential melastatin 6 and 7 channels, magnesium transport, and vascular biology: implications in hypertension.
R. M. Touyz (2008)
Am J Physiol Heart Circ Physiol 294, H1103-H1118
   Abstract »    Full Text »    PDF »
Role of Mitochondrial Dysfunction in Insulin Resistance.
J.-a Kim, Y. Wei, and J. R. Sowers (2008)
Circ. Res. 102, 401-414
   Abstract »    Full Text »    PDF »
Mitochondrial Dysfunction in the Hypertensive Rat Brain: Respiratory Complexes Exhibit Assembly Defects in Hypertension.
A. Lopez-Campistrous, L. Hao, W. Xiang, D. Ton, P. Semchuk, J. Sander, M. J. Ellison, and C. Fernandez-Patron (2008)
Hypertension 51, 412-419
   Abstract »    Full Text »    PDF »
Direct linkage of mitochondrial genome variation to risk factors for type 2 diabetes in conplastic strains.
M. Pravenec, M. Hyakukoku, J. Houstek, V. Zidek, V. Landa, P. Mlejnek, I. Miksik, K. Dudova-Mothejzikova, P. Pecina, M. Vrbacky, et al. (2007)
Genome Res. 17, 1319-1326
   Abstract »    Full Text »    PDF »
Homoplasmy, heteroplasmy, and mitochondrial dystonia.
R. McFarland, P. F. Chinnery, E. L. Blakely, A. M. Schaefer, A.A.M. Morris, S. M. Foster, H. A.L. Tuppen, V. Ramesh, P. J. Dorman, D. M. Turnbull, et al. (2007)
Neurology 69, 911-916
   Abstract »    Full Text »    PDF »
Prevalence and Characteristics of a Family History of End-Stage Renal Disease among Adults in the United States Population: Reasons for Geographic and Racial Differences in Stroke (REGARDS) Renal Cohort Study.
W. McClellan, R. Speckman, L. McClure, V. Howard, R. C. Campbell, M. Cushman, P. Audhya, G. Howard, and D. G. Warnock (2007)
J. Am. Soc. Nephrol. 18, 1344-1352
   Abstract »    Full Text »    PDF »
Mitochondrial Dysfunction in Atherosclerosis.
N. R. Madamanchi and M. S. Runge (2007)
Circ. Res. 100, 460-473
   Abstract »    Full Text »    PDF »
Developmental programming of obesity in mammals.
P. D. Taylor and L. Poston (2007)
Exp Physiol 92, 287-298
   Abstract »    Full Text »    PDF »
Sequence analysis of the complete mitochondrial DNA in 10 commonly used inbred rat strains.
N. E. Schlick, M. I. Jensen-Seaman, K. Orlebeke, A. E. Kwitek, H. J. Jacob, and J. Lazar (2006)
Am J Physiol Cell Physiol 291, C1183-C1192
   Abstract »    Full Text »    PDF »
Magnesium and muscle performance in older persons: the InCHIANTI study..
L. J Dominguez, M. Barbagallo, F. Lauretani, S. Bandinelli, A. Bos, A. M. Corsi, E. M Simonsick, and L. Ferrucci (2006)
Am. J. Clinical Nutrition 84, 419-426
   Abstract »    Full Text »    PDF »
Renal mitochondrial dysfunction in spontaneously hypertensive rats is attenuated by losartan but not by amlodipine.
E. M. V. de Cavanagh, J. E. Toblli, L. Ferder, B. Piotrkowski, I. Stella, and F. Inserra (2006)
Am J Physiol Regulatory Integrative Comp Physiol 290, R1616-R1625
   Abstract »    Full Text »    PDF »
Hypertension, Kidney, and Transgenics: A Fresh Perspective.
L. J. Mullins, M. A. Bailey, and J. J. Mullins (2006)
Physiol Rev 86, 709-746
   Abstract »    Full Text »    PDF »
The Novel A4435G Mutation in the Mitochondrial tRNAMet May Modulate the Phenotypic Expression of the LHON-Associated ND4 G11778A Mutation.
J. Qu, R. Li, X. Zhou, Y. Tong, F. Lu, Y. Qian, Y. Hu, J. Q. Mo, C. E. West, and M.-X. Guan (2006)
Invest. Ophthalmol. Vis. Sci. 47, 475-483
   Abstract »    Full Text »    PDF »
Peroxisome proliferator-activated receptor gamma and its coactivator-1 alpha may be associated with features of the metabolic syndrome in adolescents.
S Sookoian, S I Garcia, P I Porto, G Dieuzeide, C D Gonzalez, and C J Pirola (2005)
J. Mol. Endocrinol. 35, 373-380
   Abstract »    Full Text »    PDF »
Estrogen Increases Mitochondrial Efficiency and Reduces Oxidative Stress in Cerebral Blood Vessels.
C. Stirone, S. P. Duckles, D. N. Krause, and V. Procaccio (2005)
Mol. Pharmacol. 68, 959-965
   Abstract »    Full Text »    PDF »
Association of Mitochondrial Deoxyribonucleic Acid 16189 Variant (T->C Transition) with Metabolic Syndrome in Chinese Adults.
S.-W. Weng, C.-W. Liou, T.-K. Lin, Y.-H. Wei, C.-F. Lee, H.-L. Eng, S.-D. Chen, R.-T. Liu, J.-F. Chen, I-Y. Chen, et al. (2005)
J. Clin. Endocrinol. Metab. 90, 5037-5040
   Abstract »    Full Text »    PDF »
Protection in the aged heart: preventing the heart-break of old age?.
M. Juhaszova, C. Rabuel, D. B. Zorov, E. G. Lakatta, and S. J. Sollott (2005)
Cardiovasc Res 66, 233-244
   Abstract »    Full Text »    PDF »
Highlights from the literature.
(2005)
Physiology 20, 3-9
   Full Text »    PDF »
Cardiovascular Risk Factors Emerge After Artificial Selection for Low Aerobic Capacity.
U. Wisloff, S. M. Najjar, O. Ellingsen, P. M. Haram, S. Swoap, Q. Al-Share, M. Fernstrom, K. Rezaei, S. J. Lee, L. G. Koch, et al. (2005)
Science 307, 418-420
   Abstract »    Full Text »    PDF »
Mitochondrial Gene Mutation Mimics Part of the Metabolic Syndrome.
(2004)
Journal Watch Dermatology 2004, 6
   Full Text »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)