Mitochondrial Lon protease is a human stress protein

Ngo, Jenny K.; Davies, Kelvin J.A.

doi:10.1016/j.freeradbiomed.2008.12.024

Cited by 114 publications

(108 citation statements)

References 51 publications

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“…Thus, the effects of Lon depletion may be species-or cell type-specific. As in a recent report with human rhabdomyosarcoma cells (39), depletion of Lon protease in Drosophila Schneider cells results in an increase in the levels of oxidized proteins in mitochondria, indicating that Lon is responsible for degradation of oxidized mitochondrial proteins, and suggesting that variations in cell viability as a result of Lon depletion may reflect varying cellular tolerances for oxidative damage to mitochondrial proteins.…”

Section: Discussionsupporting

confidence: 60%

Mitochondrial Lon protease regulates mitochondrial DNA copy number and transcription by selective degradation of mitochondrial transcription factor A (TFAM)

Matsushima

Goto

Kaguni

2010

Proc. Natl. Acad. Sci. U.S.A.

250

220

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Lon is the major protease in the mitochondrial matrix in eukaryotes, and is well conserved among species. Although a role for Lon in mitochondrial biogenesis has been proposed, the mechanistic basis is unclear. Here, we demonstrate a role for Lon in mtDNA metabolism. An RNA interference (RNAi) construct was designed that reduces Lon to less than 10% of its normal level in Drosophila Schneider cells. RNAi knockdown of Lon results in increased abundance of mitochondrial transcription factor A (TFAM) and mtDNA copy number. In a corollary manner, overexpression of Lon reduces TFAM levels and mtDNA copy number. Notably, induction of mtDNA depletion in Lon knockdown cells does not result in degradation of TFAM, thereby causing a dramatic increase in the TFAM∶mtDNA ratio. The increased TFAM∶mtDNA ratio in turn causes inhibition of mitochondrial transcription. We conclude that Lon regulates mitochondrial transcription by stabilizing the mitochondrial TFAM∶ mtDNA ratio via selective degradation of TFAM.AAA+ protease | mtDNA maintenance | quality control

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Section: Discussionsupporting

confidence: 60%

Mitochondrial Lon protease regulates mitochondrial DNA copy number and transcription by selective degradation of mitochondrial transcription factor A (TFAM)

Matsushima

Goto

Kaguni

2010

Proc. Natl. Acad. Sci. U.S.A.

250

220

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“…Further study revealed that the ROSinduced degradation of UNG1 was not proteasome dependent; rather, LonP1 was responsible for UNG1 degradation under oxidative stress. LonP1 is a mitochondrial ATP-dependent protease [50], which is induced by oxidative stress to degrade oxidized proteins within the mitochondrial matrix [50][51][52][53][54]. Although the molecular mechanisms leading to degradation of UNG1 are still not clear, our study reveals that ROS promotesLonP1-dependent UNG1 degradation whereas the UNG1-PRDX3 interaction protects UNG1 from ROS-mediated degradation.…”

Section: Discussionmentioning

confidence: 66%

Hydrogen peroxide mediated mitochondrial UNG1-PRDX3 interaction and UNG1 degradation

Liu

Gong

et al. 2016

Free Radical Biology and Medicine

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“…Specific thioredoxin, TrxR and Grx isoforms localize to mitochondria in mammalian, and presumably avian, cells (see Page et al 2010b). Similarly, mitochondria contain a Lon protease with similar stress-inducible protein degradation functions to the 20S/26S proteasome (Ngo and Davies 2009). These specific mitochondrial activities may be upregulated concomitantly with increased longevity, a possibility that should be explored in future studies.…”

Section: Discussionmentioning

confidence: 99%

Enhanced protein repair and recycling are not correlated with longevity in 15 vertebrate endotherm species

Salway

Page

Faure

et al. 2010

AGE

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Previous studies have shown that longevity is associated with enhanced cellular stress resistance. This observation supports the disposable soma theory of aging, which suggests that the investment made in cellular maintenance will be proportional to selective pressures to extend lifespan. Maintenance of protein homeostasis is a critical component of cellular maintenance and stress resistance. To test the hypothesis that enhanced protein repair and recycling activities underlie longevity, we measured the activities of the 20S/26S proteasome and two protein repair enzymes in liver, heart and brain tissues of 15 different mammalian and avian species with maximum lifespans (MLSP) ranging from 3 to 30 years. The data set included Snell dwarf mice, in which lifespan is increased by ∼50% compared to their normal littermates. None of these activities in any of the three tissues correlated positively with MLSP. In liver, 20S/26S proteasome and thioredoxin reductase (TrxR) activities correlated negatively with body mass. In brain tissue, TrxR was also negatively correlated with body mass. Glutaredoxin (Grx) activity in brain was negatively correlated with MLSP and this correlation remained after residual analysis to remove the effects of body mass, but was lost when the data were analysed using Felsenstein's independent contrasts. Snell dwarf mice had marginally lower 20S proteasome, TrxR and Grx activities than normal controls in brain, but not heart tissue. Thus, increased longevity is not associated with increased protein repair or proteasomal degradation capacities in vertebrate endotherms.

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Mitochondrial Lon protease is a human stress protein

Cited by 114 publications

References 51 publications

Mitochondrial Lon protease regulates mitochondrial DNA copy number and transcription by selective degradation of mitochondrial transcription factor A (TFAM)

Mitochondrial Lon protease regulates mitochondrial DNA copy number and transcription by selective degradation of mitochondrial transcription factor A (TFAM)

Hydrogen peroxide mediated mitochondrial UNG1-PRDX3 interaction and UNG1 degradation

Enhanced protein repair and recycling are not correlated with longevity in 15 vertebrate endotherm species

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