Mitochondrial proline catabolism activates Ras1/cAMP/PKA-induced filamentation in Candida albicans.
Amino acids are among the earliest identified inducers of yeast-to-hyphal transitions in Candida albicans, an opportunistic fungal pathogen of humans. Here, we show that the morphogenic amino acids arginine, ornithine and proline are internalized and metabolized in mitochondria via a PUT1- and PUT2-...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-02-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC6386415?pdf=render |
| _version_ | 1818962349985366016 |
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| author | Fitz Gerald S Silao Meliza Ward Kicki Ryman Axel Wallström Björn Brindefalk Klas Udekwu Per O Ljungdahl |
| author_facet | Fitz Gerald S Silao Meliza Ward Kicki Ryman Axel Wallström Björn Brindefalk Klas Udekwu Per O Ljungdahl |
| author_sort | Fitz Gerald S Silao |
| collection | DOAJ |
| description | Amino acids are among the earliest identified inducers of yeast-to-hyphal transitions in Candida albicans, an opportunistic fungal pathogen of humans. Here, we show that the morphogenic amino acids arginine, ornithine and proline are internalized and metabolized in mitochondria via a PUT1- and PUT2-dependent pathway that results in enhanced ATP production. Elevated ATP levels correlate with Ras1/cAMP/PKA pathway activation and Efg1-induced gene expression. The magnitude of amino acid-induced filamentation is linked to glucose availability; high levels of glucose repress mitochondrial function thereby dampening filamentation. Furthermore, arginine-induced morphogenesis occurs more rapidly and independently of Dur1,2-catalyzed urea degradation, indicating that mitochondrial-generated ATP, not CO2, is the primary morphogenic signal derived from arginine metabolism. The important role of the SPS-sensor of extracellular amino acids in morphogenesis is the consequence of induced amino acid permease gene expression, i.e., SPS-sensor activation enhances the capacity of cells to take up morphogenic amino acids, a requisite for their catabolism. C. albicans cells engulfed by murine macrophages filament, resulting in macrophage lysis. Phagocytosed put1-/- and put2-/- cells do not filament and exhibit reduced viability, consistent with a critical role of mitochondrial proline metabolism in virulence. |
| first_indexed | 2024-12-20T12:27:55Z |
| format | Article |
| id | doaj.art-cdb21f4f35394bdf9f5442c2e4a52657 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-20T12:27:55Z |
| publishDate | 2019-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-cdb21f4f35394bdf9f5442c2e4a526572022-12-21T19:40:49ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042019-02-01152e100797610.1371/journal.pgen.1007976Mitochondrial proline catabolism activates Ras1/cAMP/PKA-induced filamentation in Candida albicans.Fitz Gerald S SilaoMeliza WardKicki RymanAxel WallströmBjörn BrindefalkKlas UdekwuPer O LjungdahlAmino acids are among the earliest identified inducers of yeast-to-hyphal transitions in Candida albicans, an opportunistic fungal pathogen of humans. Here, we show that the morphogenic amino acids arginine, ornithine and proline are internalized and metabolized in mitochondria via a PUT1- and PUT2-dependent pathway that results in enhanced ATP production. Elevated ATP levels correlate with Ras1/cAMP/PKA pathway activation and Efg1-induced gene expression. The magnitude of amino acid-induced filamentation is linked to glucose availability; high levels of glucose repress mitochondrial function thereby dampening filamentation. Furthermore, arginine-induced morphogenesis occurs more rapidly and independently of Dur1,2-catalyzed urea degradation, indicating that mitochondrial-generated ATP, not CO2, is the primary morphogenic signal derived from arginine metabolism. The important role of the SPS-sensor of extracellular amino acids in morphogenesis is the consequence of induced amino acid permease gene expression, i.e., SPS-sensor activation enhances the capacity of cells to take up morphogenic amino acids, a requisite for their catabolism. C. albicans cells engulfed by murine macrophages filament, resulting in macrophage lysis. Phagocytosed put1-/- and put2-/- cells do not filament and exhibit reduced viability, consistent with a critical role of mitochondrial proline metabolism in virulence.http://europepmc.org/articles/PMC6386415?pdf=render |
| spellingShingle | Fitz Gerald S Silao Meliza Ward Kicki Ryman Axel Wallström Björn Brindefalk Klas Udekwu Per O Ljungdahl Mitochondrial proline catabolism activates Ras1/cAMP/PKA-induced filamentation in Candida albicans. PLoS Genetics |
| title | Mitochondrial proline catabolism activates Ras1/cAMP/PKA-induced filamentation in Candida albicans. |
| title_full | Mitochondrial proline catabolism activates Ras1/cAMP/PKA-induced filamentation in Candida albicans. |
| title_fullStr | Mitochondrial proline catabolism activates Ras1/cAMP/PKA-induced filamentation in Candida albicans. |
| title_full_unstemmed | Mitochondrial proline catabolism activates Ras1/cAMP/PKA-induced filamentation in Candida albicans. |
| title_short | Mitochondrial proline catabolism activates Ras1/cAMP/PKA-induced filamentation in Candida albicans. |
| title_sort | mitochondrial proline catabolism activates ras1 camp pka induced filamentation in candida albicans |
| url | http://europepmc.org/articles/PMC6386415?pdf=render |
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