Open AccessMitochondrial dysfunction leads to telomere attrition and genomic instability
Author(s) -
Liu Lin,
Trimarchi James R.,
Smith Peter J. S.,
Keefe David L.
Publication year - 2002
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1046/j.1474-9728.2002.00004.x
Subject(s) - telomere , genome instability , biology , senescence , mitochondrion , mitochondrial dna , telomerase , chromosome instability , oxidative stress , genetics , microbiology and biotechnology , dna damage , chromosome , gene , dna , endocrinology
Summary Mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence, apoptosis, aging and aging‐associated pathologies. Telomere shortening and genomic instability have also been associated with replicative senescence, aging and cancer. Here we show that mitochondrial dysfunction leads to telomere attrition, telomere loss, and chromosome fusion and breakage, accompanied by apoptosis. An antioxidant prevented telomere loss and genomic instability in cells with dysfunctional mitochondria, suggesting that reactive oxygen species are mediators linking mitochondrial dysfunction and genomic instability. Further, nuclear transfer protected genomes from telomere dysfunction and promoted cell survival by reconstitution with functional mitochondria. This work links mitochondrial dysfunction and genomic instability and may provide new therapeutic strategies to combat certain mitochondrial and aging‐associated pathologies.