Mitochondrial DNA repair and aging

被引:245
作者
Mandavilli, BS [1 ]
Santos, JH [1 ]
Van Houten, B [1 ]
机构
[1] NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA
关键词
mitochondria; DNA damage; DNA repair; animal models; C; elegans; Drosophila; yeast;
D O I
10.1016/S0027-5107(02)00220-8
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The mitochondrial electron transport chain plays an important role in energy production in aerobic organisms and is also a significant source of reactive oxygen species that damage DNA, RNA and proteins in the cell. Oxidative damage to the mitochondrial DNA is implicated in various degenerative diseases, cancer and aging. The importance of mitochondrial ROS in age-related degenerative diseases is further strengthened by studies using animal models, Caenorhabditis elegans, Drosophila and yeast. Research in the last several years shows that mitochondrial DNA is more susceptible to various carcinogens and ROS when compared to nuclear DNA. DNA damage in mammalian mitochondria is repaired by base excision repair (BER). Studies have shown that mitochondria contain all the enzymes required for BER. Mitochondrial DNA damage, if not repaired, leads to disruption of electron transport chain and production of more ROS. This vicious cycle of ROS production and mtDNA damage ultimately leads to energy depletion in the cell and apoptosis. Published by Elsevier Science B.V.
引用
收藏
页码:127 / 151
页数:25
相关论文
共 253 条
[1]   COVALENT BINDING OF POLYCYCLIC AROMATIC-COMPOUNDS TO MITOCHONDRIAL AND NUCLEAR-DNA [J].
ALLEN, JA ;
COOMBS, MM .
NATURE, 1980, 287 (5779) :244-245
[2]  
Alseth I, 1999, MOL CELL BIOL, V19, P3779
[3]   OXIDANTS, ANTIOXIDANTS, AND THE DEGENERATIVE DISEASES OF AGING [J].
AMES, BN ;
SHIGENAGA, MK ;
HAGEN, TM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (17) :7915-7922
[4]  
ANDERSON CTM, 1980, NUCLEIC ACIDS RES, V8, P875
[5]   Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP [J].
Andreassen, OA ;
Ferrante, RJ ;
Dedeoglu, A ;
Albers, DW ;
Klivenyi, P ;
Carlson, EJ ;
Epstein, CJ ;
Beal, MF .
EXPERIMENTAL NEUROLOGY, 2001, 167 (01) :189-195
[6]  
[Anonymous], 1997, C ELEGANS
[7]   Mitochondrial endogenous oxidative damage has been overestimated [J].
Anson, RM ;
Hudson, E ;
Bohr, VA .
FASEB JOURNAL, 2000, 14 (02) :355-360
[8]   Measurement of oxidatively induced base lesions in liver from Wistar rats of different ages [J].
Anson, RM ;
Sentürker, S ;
Dizdaroglu, M ;
Bohr, VA .
FREE RADICAL BIOLOGY AND MEDICINE, 1999, 27 (3-4) :456-462
[9]   DELETERIOUS MITOCHONDRIAL-DNA MUTATIONS ACCUMULATE IN AGING HUMAN TISSUES [J].
ARNHEIM, N ;
CORTOPASSI, G .
MUTATION RESEARCH, 1992, 275 (3-6) :157-167
[10]   Increased sensitivity of homozygous SOD2 mutant mice to oxygen toxicity [J].
Asikainen, TM ;
Huang, TT ;
Taskinen, E ;
Levonen, AL ;
Carlson, E ;
Lapatto, R ;
Epstein, CJ ;
Raivio, KO .
FREE RADICAL BIOLOGY AND MEDICINE, 2002, 32 (02) :175-186