Mitochondrial DNA repair and association with aging--an update

TY - JOUR

T1 - Mitochondrial DNA repair and association with aging--an update

AU - Diaz, Ricardo Gredilla

AU - Bohr, Vilhelm A

AU - Stevnsner, Tinna V.

N1 - Copyright (c) 2010 Elsevier Inc. All rights reserved.

PY - 2010/8/1

Y1 - 2010/8/1

N2 - Mitochondrial DNA is constantly exposed to oxidative injury. Due to its location close to the main site of reactive oxygen species, the inner mitochondrial membrane, mtDNA is more susceptible than nuclear DNA to oxidative damage. The accumulation of DNA damage is thought to play a critical role in the aging process and to be particularly deleterious in post-mitotic cells. Thus, DNA repair is an important mechanism for maintenance of genomic integrity. Despite the importance of mitochondria in the aging process, it was thought for many years that mitochondria lacked an enzymatic DNA repair system comparable to that in the nuclear compartment. However, it is now well established that DNA repair actively takes place in mitochondria. Oxidative DNA damage processing, base excision repair mechanisms were the first to be described in these organelles, and consequently the best understood. However, new proteins and novel DNA repair pathways, thought to be exclusively present in the nucleus, have recently been described also to be present in mitochondria. Here we review the main mitochondrial DNA repair pathways and their association with the aging process.

AB - Mitochondrial DNA is constantly exposed to oxidative injury. Due to its location close to the main site of reactive oxygen species, the inner mitochondrial membrane, mtDNA is more susceptible than nuclear DNA to oxidative damage. The accumulation of DNA damage is thought to play a critical role in the aging process and to be particularly deleterious in post-mitotic cells. Thus, DNA repair is an important mechanism for maintenance of genomic integrity. Despite the importance of mitochondria in the aging process, it was thought for many years that mitochondria lacked an enzymatic DNA repair system comparable to that in the nuclear compartment. However, it is now well established that DNA repair actively takes place in mitochondria. Oxidative DNA damage processing, base excision repair mechanisms were the first to be described in these organelles, and consequently the best understood. However, new proteins and novel DNA repair pathways, thought to be exclusively present in the nucleus, have recently been described also to be present in mitochondria. Here we review the main mitochondrial DNA repair pathways and their association with the aging process.

KW - Aging

KW - Animals

KW - DNA Damage

KW - DNA Glycosylases

KW - DNA Ligases

KW - DNA Mismatch Repair

KW - DNA Repair

KW - DNA, Mitochondrial

KW - DNA-(Apurinic or Apyrimidinic Site) Lyase

KW - DNA-Directed DNA Polymerase

KW - Humans

KW - Mitochondria

KW - Models, Biological

KW - Reactive Oxygen Species

U2 - 10.1016/j.exger.2010.01.017

DO - 10.1016/j.exger.2010.01.017

M3 - Review

C2 - 20096766

SN - 0531-5565

VL - 45

SP - 478

EP - 488

JO - Experimental Gerontology

JF - Experimental Gerontology

IS - 7-8

ER -