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  • SHRED Is a Regulatory Cascade that Reprograms Ubr1 Substrate Specificity for Enhanced Protein Quality Control during Stress MOLECULAR CELL Szoradi, T., Schaeff, K., Garcia-Rivera, E. M., Itzhak, D. N., Schmidt, R. M., Bircham, P. W., Leiss, K., Diaz-Miyar, J., Chen, V. K., Muzzey, D., Borner, G. H., Schuck, S. 2018; 70 (6): 1025-+

    Abstract

    When faced with proteotoxic stress, cells mount adaptive responses to eliminate aberrant proteins. Adaptive responses increase the expression of protein folding and degradation factors to enhance the cellular quality control machinery. However, it is unclear whether and how this augmented machinery acquires new activities during stress. Here, we uncover a regulatory cascade in budding yeast that consists of the hydrophilin protein Roq1/Yjl144w, the HtrA-type protease Ynm3/Nma111, and the ubiquitin ligase Ubr1. Various stresses stimulate ROQ1 transcription. The Roq1 protein is cleaved by Ynm3. Cleaved Roq1 interacts with Ubr1, transforming its substrate specificity. Altered substrate recognition by Ubr1 accelerates proteasomal degradation of misfolded as well as native proteins at the endoplasmic reticulum membrane and in the cytosol. We term this pathway stress-induced homeostatically regulated protein degradation (SHRED) and propose that it promotes physiological adaptation by reprogramming a key component of the quality control machinery.

    View details for DOI 10.1016/j.molcel.2018.04.027

    View details for Web of Science ID 000436640300008

    View details for PubMedID 29861160

  • A repeat protein links Rubisco to form the eukaryotic carbon-concentrating organelle PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Mackinder, L. C., Meyer, M. T., Mettler-Altmann, T., Chen, V. K., Mitchell, M. C., Caspari, O., Rosenzweig, E. S., Pallesen, L., Reeves, G., Itakura, A., Roth, R., Sommer, F., Geimer, S., Muehlhaus, T., Schroda, M., Goodenough, U., Stitt, M., Griffiths, H., Jonikas, M. C. 2016; 113 (21): 5958-5963

    Abstract

    Biological carbon fixation is a key step in the global carbon cycle that regulates the atmosphere's composition while producing the food we eat and the fuels we burn. Approximately one-third of global carbon fixation occurs in an overlooked algal organelle called the pyrenoid. The pyrenoid contains the CO2-fixing enzyme Rubisco and enhances carbon fixation by supplying Rubisco with a high concentration of CO2 Since the discovery of the pyrenoid more that 130 y ago, the molecular structure and biogenesis of this ecologically fundamental organelle have remained enigmatic. Here we use the model green alga Chlamydomonas reinhardtii to discover that a low-complexity repeat protein, Essential Pyrenoid Component 1 (EPYC1), links Rubisco to form the pyrenoid. We find that EPYC1 is of comparable abundance to Rubisco and colocalizes with Rubisco throughout the pyrenoid. We show that EPYC1 is essential for normal pyrenoid size, number, morphology, Rubisco content, and efficient carbon fixation at low CO2 We explain the central role of EPYC1 in pyrenoid biogenesis by the finding that EPYC1 binds Rubisco to form the pyrenoid matrix. We propose two models in which EPYC1's four repeats could produce the observed lattice arrangement of Rubisco in the Chlamydomonas pyrenoid. Our results suggest a surprisingly simple molecular mechanism for how Rubisco can be packaged to form the pyrenoid matrix, potentially explaining how Rubisco packaging into a pyrenoid could have evolved across a broad range of photosynthetic eukaryotes through convergent evolution. In addition, our findings represent a key step toward engineering a pyrenoid into crops to enhance their carbon fixation efficiency.

    View details for DOI 10.1073/pnas.1522866113

    View details for Web of Science ID 000376779900061

    View details for PubMedID 27166422

    View details for PubMedCentralID PMC4889370