Plastid-produced interorgannellar stress signal MEcPP potentiates induction of the unfolded protein response in endoplasmic reticulum

Significance A defining characteristic of living organisms is dynamic alignment of cellular responses to stress through activation of signal transduction pathways essential for fine-tuning of interorgannellar communication. Uncovering these communication signals is one of the prime challenges of biology. We have identified a chloroplast-produced retrograde signal, methylerythritol cyclodiphosphate (MEcPP), as a trigger of unfolded protein response (UPR) required for restoration of protein-folding homeostasis in the endoplasmic reticulum (ER). Increased levels of MEcPP via genetic manipulation or exogenous application potentiate expression of a sub-set of UPR genes, and alter plant’s resistance to the ER stress inducing agent. These findings provide a link between a plastidial retrograde signal and transcriptional reprogramming of ER genes critical for readjustment of protein-folding capacity in stressed cells. Cellular homeostasis in response to internal and external stimuli requires a tightly coordinated interorgannellar communication network. We recently identified methylerythritol cyclodiphosphate (MEcPP) as a novel stress-specific retrograde signaling metabolite that accumulates in response to environmental perturbations to relay information from plastids to the nucleus. We now demonstrate, using a combination of transcriptome and proteome profiling approaches, that mutant plants ( ceh1 ) with high endogenous levels of MEcPP display increased transcript and protein levels for a subset of the core unfolded protein response (UPR) genes. The UPR is an adaptive cellular response conserved throughout eukaryotes to stress conditions that perturb the endoplasmic reticulum (ER) homeostasis. Our results suggest that MEcPP directly triggers the UPR. Exogenous treatment with MEcPP induces the rapid and transient induction of both the unspliced and spliced forms of the UPR gene bZIP60 . Moreover, compared with the parent background (P), ceh1 mutants are less sensitive to the ER-stress-inducing agent tunicamycin (Tm). P and ceh1 plants treated with Tm display similar UPR transcript profiles, suggesting that although MEcPP accumulation causes partial induction of selected UPR genes, full induction is triggered by accumulation of misfolded proteins. This finding refines our perspective of interorgannellar communication by providing a link between a plastidial retrograde signaling molecule and its targeted ensemble of UPR components in ER.