当前位置： SCI文献检索 > PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA期刊下所有文献 > Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues.

Clonally expanded mtDNA point mutations are abundant in individual cells of human tissues.

Abstract：

:Using single-cell sequence analysis, we discovered that a high proportion of cells in tissues as diverse as buccal epithelium and heart muscle contain high proportions of clonal mutant mtDNA expanded from single initial mutant mtDNA molecules. We demonstrate that intracellular clonal expansion of somatic point mutations is a common event in normal human tissues. This finding implies efficient homogenization of mitochondrial genomes within individual cells. Significant qualitative differences observed between the spectra of clonally expanded mutations in proliferating epithelial cells and postmitotic cardiomyocytes suggest, however, that either the processes generating these mutations or mechanisms driving them to homoplasmy are likely to be fundamentally different between the two tissues. Furthermore, the ability of somatic mtDNA mutations to expand (required for their phenotypic expression), as well as their apparently high incidence, reinforces the possibility that these mutations may be involved actively in various physiological processes such as aging and degenerative disease. The abundance of clonally expanded point mutations in individual cells of normal tissues also suggests that the recently discovered accumulation of mtDNA mutations in tumors may be explained by processes that are similar or identical to those operating in the normal tissue.

journal_name

Proc Natl Acad Sci U S A

journal_title

Proceedings of the National Academy of Sciences of the United States of America

authors

Nekhaeva E,Bodyak ND,Kraytsberg Y,McGrath SB,Van Orsouw NJ,Pluzhnikov A,Wei JY,Vijg J,Khrapko K

doi

10.1073/pnas.072670199

keywords:

subject

Has Abstract

pub_date

2002-04-16 00:00:00

pages

5521-6

issue

8

eissn

0027-8424

issn

1091-6490

pii

072670199

journal_volume

99

pub_type

杂志文章

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