Oxidation of the Yeast Mitochondrial Thioredoxin Promotes Cell Death

Greetham, Darren; Kritsiligkou, Paraskevi; Watkins, Rachel H.; Carter, Zorana; Parkin, Jill; Grant, Chris M.

doi:10.1089/ars.2012.4597

Cited by 36 publications

(39 citation statements)

References 43 publications

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“…Because reduced Trx plays a critical role in cellular proliferation and viability (Scheme 1), excessive oxidation of Trx will lead to cell death (41). Recently, a study showed that oxidation of the yeast mitochondrial thioredoxin promotes cell death (45).…”

Section: Discussionmentioning

confidence: 99%

Glutathione and Glutaredoxin Act as a Backup of Human Thioredoxin Reductase 1 to Reduce Thioredoxin 1 Preventing Cell Death by Aurothioglucose

Zhang

et al. 2012

Journal of Biological Chemistry

197

143

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Background: TrxR1 is the only known reductant of thioredoxin. Results: The glutaredoxin system showed the capacity of reducing thioredoxin 1. Depletion of both TrxR1 activity and glutathione in cells induced Trx1 oxidation and cell death. Conclusion:The glutathione/glutaredoxin system is a backup of TrxR1 for reducing thioredoxin 1. Significance: We demonstrated the critical role of the thioredoxin redox state in cell survival and a new role of glutathione.

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Section: Discussionmentioning

confidence: 99%

Glutathione and Glutaredoxin Act as a Backup of Human Thioredoxin Reductase 1 to Reduce Thioredoxin 1 Preventing Cell Death by Aurothioglucose

Zhang

et al. 2012

Journal of Biological Chemistry

197

143

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“…It is conceivable that such an intracellular redox-dependent signaling pathway dampens the propagation of mutants that produce increased levels of mitochondriaderived oxidative stress in order to prevent the distribution of malfunctional mitochondria. A recent study showed that oxidative stress in mitochondria leads to cell death in yeast by inducing caspase-mediated apoptosis (19). The yeast metacaspase Yca1 is known to be activated by hydrogen peroxide although the details of this apoptotic signaling pathway in yeast are not entirely clear (33).…”

Section: Discussionmentioning

confidence: 99%

Inaccurately Assembled CytochromecOxidase Can Lead to Oxidative Stress-Induced Growth Arrest

Bode

Longen

Morgan

et al. 2013

Antioxidants & Redox Signaling

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Aims: To identify yeast mutants that show a strong redox dependence of the ability to respire, we systematically screened a yeast deletion library for mutants that require the presence of reductants for growth on nonfermentable carbon sources. Results: Respirative growth of 44 yeast mutants was significantly improved by the addition of dithiothreitol or glutathione. Two mutants that were strongly stimulated by reductants lacked the proteins Cmc1 and Coa4. Both proteins belong to the family of ''twin Cx 9 C'' proteins present in the intermembrane space of mitochondria. Deletion of CMC1 or COA4 leads to assembly defects of cytochrome c oxidase, in particular to the lack of Cox1 and rapid degradation of Cox2 and Cox3. Interestingly, the presence of the reductants does not suppress these assembly defects and the levels of cytochrome c oxidase remain reduced. Reductants and antioxidants such as ascorbic acid rather counteract the effects of hydrogen peroxide that is produced from partially assembled cytochrome c oxidase intermediates. Innovation: Here we show that oxidative stress generated by the accumulation of partially assembled respiratory chain complexes prevents growth on carbon sources that force cells to respire. Conclusion: Defects in the assembly of cytochrome c oxidase can lead to increased production of hydrogen peroxide, which is sensed in cells and blocks their proliferation. We propose that this redox-regulated feedback regulation specifically slows down the propagation of cells carrying respiratory chain mutations in order to select for cells of high mitochondrial fitness. Antioxid. Redox Signal. 18, 1597-1612.

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“…The opening of this pore is accompanied by membrane potential (ΔΨ) collapse, calcium release, uptake of electrolytes and water, matrix swelling and ruptures of the mitochondrial outer membrane [42] . As a consequence, several factors are released into the cytosol including cytochrome c, apoptotic peptidase activating factor 1 (apaf-1), apoptosis-inducing factor (AIF) and caspase family members, which participate in apoptosis pathways [43][44][45] . Several agents, such as Ca 2+ , thiol oxidants, reactive oxygen species (ROS), and/or members of the Bcl -2 family of proteins can regulate cell death or survival by interference with MPTP opening [46][47][48] .…”

Section: Discussionmentioning

confidence: 99%

African eggplant (Solanum anguivi Lam.) fruit with bioactive polyphenolic compounds exerts in vitro antioxidant properties and inhibits Ca2+-induced mitochondrial swelling

Elekofehinti

Kamdem

Bolingon

et al. 2013

Asian Pacific Journal of Tropical Biomedicine

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Oxidation of the Yeast Mitochondrial Thioredoxin Promotes Cell Death

Abstract: Mitochondrial Prx1 functions as a redox signaling molecule that oxidizes Trx3 and promotes apoptosis. This would mean that under conditions where Prx1 cannot detoxify mitochondrial ROS, it induces cell death to remove the affected cells.

Cited by 36 publications

References 43 publications

Glutathione and Glutaredoxin Act as a Backup of Human Thioredoxin Reductase 1 to Reduce Thioredoxin 1 Preventing Cell Death by Aurothioglucose

Glutathione and Glutaredoxin Act as a Backup of Human Thioredoxin Reductase 1 to Reduce Thioredoxin 1 Preventing Cell Death by Aurothioglucose

Inaccurately Assembled CytochromecOxidase Can Lead to Oxidative Stress-Induced Growth Arrest

African eggplant (Solanum anguivi Lam.) fruit with bioactive polyphenolic compounds exerts in vitro antioxidant properties and inhibits Ca2+-induced mitochondrial swelling

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