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Adaptive aneuploidy protects against thiol peroxidase deficiency by increasing respiration via key mitochondrial proteins
Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular mil...
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Published in: | Proceedings of the National Academy of Sciences - PNAS 2015-08, Vol.112 (34), p.10685-10690 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Aerobic respiration is a fundamental energy-generating process; however, there is cost associated with living in an oxygen-rich environment, because partially reduced oxygen species can damage cellular components. Organisms evolved enzymes that alleviate this damage and protect the intracellular milieu, most notably thiol peroxidases, which are abundant and conserved enzymes that mediate hydrogen peroxide signaling and act as the first line of defense against oxidants in nearly all living organisms. Deletion of all eight thiol peroxidase genes in yeast (Δ8 strain) is not lethal, but results in slow growth and a high mutation rate. Here we characterized mechanisms that allow yeast cells to survive under conditions of thiol peroxidase deficiency. Two independent Δ8 strains increased mitochondrial content, altered mitochondrial distribution, and became dependent on respiration for growth but they were not hypersensitive to H₂O₂. In addition, both strains independently acquired a second copy of chromosome XI and increased expression of genes encoded by it. Survival of Δ8 cells was dependent on mitochondrial cytochrome-c peroxidase (CCP1) andUTH1, present on chromosome XI. Coexpression of these genes in Δ8 cells led to the elimination of the extra copy of chromosome XI and improved cell growth, whereas deletion of either gene was lethal. Thus, thiol peroxidase deficiency requires dosage compensation ofCCP1andUTH1via chromosome XI aneuploidy, wherein these proteins support hydroperoxide removal with the reducing equivalents generated by the electron transport chain. To our knowledge, this is the first evidence of adaptive aneuploidy counteracting oxidative stress. |
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ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.1505315112 |