Nucleic Acids Research Advance Access originally published online on September 16, 2008
Nucleic Acids Research 2008 36(18):5872-5881; doi:10.1093/nar/gkn592
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Nucleic Acids Research, 2008, Vol. 36, No. 18 5872-5881
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
Cosegregation of novel mitochondrial 16S rRNA gene mutations with the age-associated T414G variant in human cybrids
1Department of Molecular Cell Therapy, Center for Biotechnology and Biomedicine, Universität Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany, 2Department of Medical Biochemistry, Biology & Physics, University of Bari, Piazza Giulio Cesare, 11, 70124 - Bari, Italy and 3Dino Ferrari Center, Foundation IRCCS Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Department of Neurological Sciences, University of Milano, Via Sforza, 35, 20122 - Milano, Italy
*To whom correspondence should be addressed. Tel: +49 341 9731370; Fax: +49 341 9731379; Email: peter.seibel{at}bbz.uni-leipzig.de
Correspondence may also be addressed to Gaetano Villani, Tel: +39 080 5448534; Fax: +39 080 5448538; Email: villani{at}biochem.uniba.it
Received June 11, 2008. Revised August 13, 2008. Accepted September 3, 2008.
Ever increasing evidence has been provided on the accumulation of mutations in the mitochondrial DNA (mtDNA) during the aging process. However, the lack of direct functional consequences of the mutant mtDNA load on the mitochondria-dependent cell metabolism has raised many questions on the physiological importance of the age-related mtDNA variations. In the present work, we have analyzed the bioenergetic properties associated with the age-related T414G mutation of the mtDNA control region in transmitochondrial cybrids. The results show that the T414G mutation does not cause per se any detectable bioenergetic change. Moreover, three mtDNA mutations clustered in the 16S ribosomal RNA gene cosegregated together with the T414G in the same cybrid cell line. Two of them, namely T1843C and A1940G, are novel and associate with a negative bioenergetic phenotype. The results are discussed in the more general context of the complex heterogeneity and the dramatic instability of the mitochondrial genome during cell culture of transmitochondrial cybrids.