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An ongoing scientific journey to understand how photosynthetic organisms deal with damaged proteins and membranes in their most unique compartment, the chloroplast

Life on Earth crucially depends on photosynthesis –the process by which the energy of sunlight is harnessed, converting atmospheric carbon dioxide and water into sugars and oxygen. In plants and algae, photosynthesis occurs in a specialized cell compartment, the chloroplast, where complex molecular machines absorb light and channel its energy into chemical reactions. These machines are almost entirely composed of proteins that have to be quickly assembled and replaced when damaged.           

We discovered that, when overloaded with misfolded proteins, the chloroplast sends signals to activate an evolutionarily conserved nuclear gene expression program, dubbed the “chloroplast unfolded protein response” (or cpUPR for short), leading to the production of specialized factors that help protect and repair the chloroplast (1).

Through a forward genetic screen in the green alga Chlamydomonas reinhardtii, we identified Mars1, a previously uncharacterized protein kinase, as the first essential signaling component of this novel intracellular communication route (2). Lack of cpUPR induction in MARS1 mutant cells impairs their ability to cope with chloroplast stress, including exposure to excessive light –a condition where the production of unstable oxygen molecules makes chloroplast proteins particularly vulnerable to damage. These findings highlight the physiological importance of the chloroplast unfolded protein response in mitigating chloroplast proteotoxic stress.

We are currently advancing our mechanistic understanding of the cpUPR by focusing on three synergistic aims: the structural and functional dissection of Mars1, the identification of other cpUPR signaling components, and the investigation of the many yet-uncharacterized genes activated during the cpUPR.                        

Our ultimate goal is to unravel how the presence of unfolded proteins inside the chloroplast is sensed, how the signals are transduced across compartmental boundaries, and to what extent the genes activated during this response help plant cells to adapt to stress.

References:

1) Ramundo S, Casero D, Mühlhaus T, Hemme D, Sommer F, Crèvecoeur M, Rahire M, Schroda M, Rusch J, Goodenough U, Pellegrini M, Perez-Perez ME, Crespo JL, Schaad O, Civic N, Rochaix JD. (2014). Conditional Depletion of the Chlamydomonas Chloroplast ClpP Protease Activates Nuclear Genes Involved in Autophagy and Plastid Protein Quality Control. Plant Cell. 26(5):2201-2222. doi: 10.1105/tpc.114.124842. PMID: 24879428

2) Perlaza K, Toutkoushian H, Boone M, Lam M, Iwai M, Jonikas MC, Walter P, Ramundo S. (2019). The Mars1 kinase confers photoprotection through signaling in the chloroplast unfolded protein response. eLife. 2019;8:e49577. doi: 10.7554/eLife.49577. PMID: 31612858