Mitochondrial oxidative stress can lead to nuclear hypermutability

Hartman, Phil S.; Ponder, Rebecca G.; Lo, Herng-Hsiang; Ishii, Naoaki

doi:10.1016/j.mad.2004.02.007

Cited by 45 publications

(34 citation statements)

References 21 publications

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“…Taken together, these results would suggest that the mev-1 phenotype was present in our introgressed strains. Although we have not directly measured steady-state free radical production (e.g., Senoo-Matsuda et al 2001) or oxidative damage (e.g., Hartman et al 2004) in our introgressed mev-1 lines, such findings are consistently accompanied by reduced life span and/or reduced fecundity (e.g., Ishii et al 1990;Adachi et al 1998;Yanase et al 2002).…”

Section: Discussionmentioning

confidence: 86%

“…The consequences of oxidative stress on DNA structure and repair pathways for DNA oxidative damage are well characterized (Hsie et al 1986;Demple and Harrison 1994;Gille and Van Berkel 1994;Halliwell and Gutteridge 1999;Guetens et al 2002;Evans and Cooke 2004) as are the links between oxidative stress and mutation in the soma (e.g., Dollé et al 2000;Busuttil et al 2003Busuttil et al , 2005Hill et al 2005;Busuttil et al 2007;Crabbe and Hill 2010). The oxidative stress that accompanies the mev-1(kn1) mutation is considered to be mutagenic, as indicated by increased transformation rates in a transgenic mouse cell line with the equivalent mutation (Ishii et al 2005) and elevated mutation rates in the fem-3 reporter system in C. elegans (Hartman et al 2001(Hartman et al , 2004. The higher nuclear mutation rates reported in mev-1 nematodes relative to wild type (Hartman et al 2001(Hartman et al , 2004) relied on scoring visible revertants of a temperature-dependent sterile mutant at the fem-3 locus.…”

Section: Discussionmentioning

confidence: 99%

“…The oxidative stress that accompanies the mev-1(kn1) mutation is considered to be mutagenic, as indicated by increased transformation rates in a transgenic mouse cell line with the equivalent mutation (Ishii et al 2005) and elevated mutation rates in the fem-3 reporter system in C. elegans (Hartman et al 2001(Hartman et al , 2004. The higher nuclear mutation rates reported in mev-1 nematodes relative to wild type (Hartman et al 2001(Hartman et al , 2004) relied on scoring visible revertants of a temperature-dependent sterile mutant at the fem-3 locus. There is no reason to suspect an interaction between mev-1 and fem-3 that would atypically inflate the mutation rate at fem-3.…”

Section: Discussionmentioning

confidence: 99%

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No Evidence of Elevated Germline Mutation Accumulation Under Oxidative Stress in Caenorhabditis elegans

et al. 2011

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Variation in rates of molecular evolution has been attributed to numerous, interrelated causes, including metabolic rate, body size, and generation time. Speculation concerning the influence of metabolic rate on rates of evolution often invokes the putative mutagenic effects of oxidative stress. To isolate the effects of oxidative stress on the germline from the effects of metabolic rate, generation time, and other factors, we allowed mutations to accumulate under relaxed selection for 125 generations in two strains of the nematode Caenorhabditis elegans, the canonical wild-type strain (N2) and a mutant strain with elevated steady-state oxidative stress (mev-1). Contrary to our expectation, the mutational decline in fitness did not differ between N2 and mev-1. This result suggests that the mutagenic effects of oxidative stress in C. elegans are minor relative to the effects of other types of mutations, such as errors during DNA replication. However, mev-1 MA lines did go extinct more frequently than wild-type lines; some possible explanations for the difference in extinction rate are discussed. Lanfear et al. 2007;and Galtier et al. 2009). Usually, it is supposed that organisms with high metabolic rates have higher rates of mutation, and thus faster rates of evolution, than do organisms with low metabolic rates. There are two (not mutually exclusive) ways by which metabolic rate might affect mutation rate. First, organisms with high metabolic rates have shorter generation times (Savage et al. 2004;Bromham 2009) and thus undergo relatively more rounds of DNA replication per generation (Laird et al. 1969;Ellegren 2007;Nikolaev et al. 2007;Thomas et al. 2010) than do organisms with low metabolic rates. If most mutations occur during DNA replication, a positive relationship between metabolic rate and mutation rate, and thus rates of evolution, is expected. Second, the oxygen-centered free radicals that are by-products of aerobic metabolism (Boveris and Chance 1973;Fridovich 2004) can cause oxidative damage to DNA (Hsie et al.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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No Evidence of Elevated Germline Mutation Accumulation Under Oxidative Stress in Caenorhabditis elegans

et al. 2011

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“…An increased production of reactive oxygen species, often associated with MRC dysfunction, can precipitate premature aging, cause mutations in the mitochondrial and nuclear genomes, and shorten lifespan (Hartman et al, 2004). The first C. elegans mtDNA deletions detected were spontaneous events in an aging, wild type population (Melov et al, 1994;Melov et al, 1995).…”

Section: Mtdna and Agingmentioning

confidence: 99%

Mitochondrial genetics

Lemire¹

2005

WormBook

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“…Studies of mutations affecting the lifespan in C. elegans as well as systematic screens of C. elegans genes using dsRNA (feeding RNAi) suggest that mitochondria and mitochondrial generation of reactive oxygen species (ROS) have a major causative role in the aging process (Shinohara et al ., 1998;Lee et al ., 2003;Turrens, 2003;Hartman et al ., 2004;Nakai et al ., 2004). There is strong evidence that caloric flux results in increased ROS formation, and that caloric restriction prolongs lifespan by decreasing ROS production via increased expression of PHA-4/Foxa, a dietary restrictionspecific activator of sod-1 , -2 , -4 , and -5 expression (Panowski et al ., 2007).…”

Section: Introductionmentioning

confidence: 99%

Glyoxalase‐1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans

et al. 2008

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SummaryStudies of mutations affecting lifespan in Caenorhabditis elegans show that mitochondrial generation of reactive oxygen species (ROS) plays a major causative role in organismal aging. Here, we describe a novel mechanism for regulating mitochondrial ROS production and lifespan in C . elegans : progressive mitochondrial protein modification by the glycolysis-derived dicarbonyl metabolite methylglyoxal (MG). We demonstrate that the activity of glyoxalase-1, an enzyme detoxifying MG, is markedly reduced with age despite unchanged levels of glyoxalase-1 mRNA. The decrease in enzymatic activity promotes accumulation of MG-derived adducts and oxidative stress markers, which cause further inhibition of glyoxalase-1 expression. Over-expression of the C . elegans glyoxalase-1 orthologue CeGly decreases MG modifications of mitochondrial proteins and mitochondrial ROS production, and prolongs C . elegans lifespan. In contrast, knock-down of CeGly increases MG modifications of mitochondrial proteins and mitochondrial ROS production, and decreases C . elegans lifespan.

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Mitochondrial oxidative stress can lead to nuclear hypermutability

Cited by 45 publications

References 21 publications

No Evidence of Elevated Germline Mutation Accumulation Under Oxidative Stress in Caenorhabditis elegans

No Evidence of Elevated Germline Mutation Accumulation Under Oxidative Stress in Caenorhabditis elegans

Mitochondrial genetics

Glyoxalase‐1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans

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