Copper homeostasis and aging in the fungal model system Podospora anserina: differential expression of PaCtr3 encoding a copper transporter
Lifespan extension of Podospora anserina mutant grisea is caused by a loss-of-function mutation in the nuclear gene Grisea. This gene encodes the copper regulated transcription factor GRISEA recently shown to be involved in the expression of PaSod2 encoding the mitochondrial manganese superoxide dis...
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Published in | The international journal of biochemistry & cell biology Vol. 34; no. 11; pp. 1355 - 1371 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier Ltd
01.11.2002
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Subjects | |
Online Access | Get full text |
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Summary: | Lifespan extension of
Podospora anserina mutant grisea is caused by a loss-of-function mutation in the nuclear gene
Grisea. This gene encodes the copper regulated transcription factor GRISEA recently shown to be involved in the expression of
PaSod2 encoding the mitochondrial manganese superoxide dismutase. Here we report the identification and characterization of a second target gene. This gene,
PaCtr3, encodes a functional homologue of the
Saccharomyces cerevisiae high affinity copper permease yCTR3.
PaCtr3 is not expressed in the grisea mutant confirming the assumption that the extension of lifespan is primarily caused by cellular copper limitation and a switch from a cytochrome oxidase (COX)-dependent to and alternative oxidase (AOX)-dependent respiration. Transcript levels of
PaCtr3 and
PaSod2 respond to copper, iron, manganese and zinc. Transcription of
PaCtr3 was found to be down-regulated during senescence of wild-type cultures suggesting that the intracellular copper concentration is raised in old cultures. A two hybrid analysis suggested that GRISEA acts as a homodimer. In accordance, an inverted repeat was identified as a putative binding sequence in the promoter region of
PaCtr3 and of
PaSod2. Finally, the expression of
PaCtr3 in transformants of the grisea mutant led to lifespan shortening. This effect correlates with the activity of the copper-dependent COX demonstrating a strong link between copper-uptake, respiration and lifespan. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1357-2725 1878-5875 |
DOI: | 10.1016/S1357-2725(02)00078-X |