When chlamydomonas reinhardtii is faced with copper-deficiency, it alters the composition of a major metabolic pathway, photosynthesis, by replacing a copper protein, plastocyanin, with a heme protein, cytochrome c6. Cyt C6 is produced by transcriptional activation of the Cyc6 gene through associated copper-response elements while loss of plastocyanin is by regulated proteolysis of the apoprotein. Other adaptive processes which occur coordinately include transcriptional activation of Cpxl, encoding coproporphyrinogen oxidase - a heme biosynthesis enzyme, and Crdl, a novel diiron enzyme which is hypothesized to be involved in plastid iron mobilization, perhaps as a back-up version of a plastidlocalized, multi-copper oxidase. A copper uptake pathway involving a reductase and a transporter is also induced. Mutations at the CRR1 locus define a master regulator of copper-responsive signal transduction. This regulatory molecule appears to be involved also in the organism's response to hypoxia by serving as a Cu(II)-based redox sensor. This system provides a unique opportunity to understand and discover cellular processes occurring during copper homeostasis in the context of deficiency. In humans, copper deficiency can result from poor nutrition, especially in infants, or from genetic diseases in copper metabolism, such as Menkes disease. The objectives of this study are: 1) to deduce the function of Crdl, the putative diiron enzyme, and its homolog, Cthl, through determination of the reaction they catalyze, their sub-organellar location and pattern of expression, assessment of whether Crdl is a back-up for a copper enzyme, phenotypic analysis of crdl mutant strains, and their comparison to iron-deficient cells; 2) to understand the function of Chlamydomonas ceruloplasmins, to analyze the operation and utilization of copper enzymes in respiration vs. photosynthesis vs. iron metabolism during adaptation of C. reinhardtii to copper-deficiency, and to discover new copper-responsive targets and copper-metabolizing proteins; and 3) to identify a key regulator, Crrl, in the copper-responsive signal transduction pathway by complementation of the crrl mutant, and to determine its mechanism of function by biochemical analysis of the expressed proteins, especially dissection of its copper-responding domains.
| Kumar, Dhivya; Strenkert, Daniela; Patel-King, Ramila S et al. (2017) A bioactive peptide amidating enzyme is required for ciliogenesis. Elife 6: |
| Blaby-Haas, Crysten E; Merchant, Sabeeha S (2017) Regulating cellular trace metal economy in algae. Curr Opin Plant Biol 39:88-96 |
| Reyes, Vincent C; Spitzmiller, Melissa R; Hong-Hermesdorf, Anne et al. (2016) Copper status of exposed microorganisms influences susceptibility to metallic nanoparticles. Environ Toxicol Chem 35:1148-58 |
| Blaby-Haas, Crysten E; Castruita, Madeli; Fitz-Gibbon, Sorel T et al. (2016) Ni induces the CRR1-dependent regulon revealing overlap and distinction between hypoxia and Cu deficiency responses in Chlamydomonas reinhardtii. Metallomics 8:679-91 |
| Strenkert, Daniela; Limso, Clariss Ann; Fatihi, Abdelhak et al. (2016) Genetically Programmed Changes in Photosynthetic Cofactor Metabolism in Copper-deficient Chlamydomonas. J Biol Chem 291:19118-31 |
| Kumar, Dhivya; Blaby-Haas, Crysten E; Merchant, Sabeeha S et al. (2016) Early eukaryotic origins for cilia-associated bioactive peptide-amidating activity. J Cell Sci 129:943-56 |
| Barahimipour, Rouhollah; Strenkert, Daniela; Neupert, Juliane et al. (2015) Dissecting the contributions of GC content and codon usage to gene expression in the model alga Chlamydomonas reinhardtii. Plant J 84:704-17 |
| Yang, Wenqiang; Wittkopp, Tyler M; Li, Xiaobo et al. (2015) Critical role of Chlamydomonas reinhardtii ferredoxin-5 in maintaining membrane structure and dark metabolism. Proc Natl Acad Sci U S A 112:14978-83 |
| Pérez-Martín, Marta; Blaby-Haas, Crysten E; Pérez-Pérez, María Esther et al. (2015) Activation of Autophagy by Metals in Chlamydomonas reinhardtii. Eukaryot Cell 14:964-73 |
| Kropat, Janette; Gallaher, Sean D; Urzica, Eugen I et al. (2015) Copper economy in Chlamydomonas: prioritized allocation and reallocation of copper to respiration vs. photosynthesis. Proc Natl Acad Sci U S A 112:2644-51 |
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