The retrograde signaling protein GUN1 regulates tetrapyrrole biosynthesis

Abstract

The biogenesis of the photosynthetic apparatus in developing seedlings requires the assembly of proteins encoded on both nuclear and chloroplast genomes. To coordinate this process there needs to be communication between these organelles, but the retrograde signals by which the chloroplast communicates with the nucleus at this time are still essentially unknown. The Arabidopsis thaliana genomes uncoupled (gun) mutants, that show elevated nuclear gene expression after chloroplast damage, have formed the basis of our understanding of retrograde signaling. Of the 6 reported gun mutations, 5 are in tetrapyrrole biosynthesis proteins and this has led to the development of a model for chloroplast-to-nucleus retrograde signaling in which ferrochelatase 1 (FC1)-dependent heme synthesis generates a positive signal promoting expression of photosynthesis-related genes. However, the molecular consequences of the strongest of the gun mutants, gun1, are poorly understood, preventing the development of a unifying hypothesis for chloroplast-to-nucleus signaling. Here, we show that GUN1 directly binds to heme and other porphyrins, reduces flux through the tetrapyrrole biosynthesis pathway to limit heme and protochlorophyllide synthesis, and can increase the chelatase activity of FC1. These results raise the possibility that the signaling role of GUN1 may be manifested through changes in tetrapyrrole metabolism, supporting a role for tetrapyrroles as mediators of a single biogenic chloroplast-to-nucleus retrograde signaling pathway.

Plastid gene expression is required for singlet oxygen-induced chloroplast degradation and cell death

“…Instead, fc2-1 gun1-9 mutants appear to suffer enhanced photo-damage. This appears to be due to an increase of tetrapyrrole synthesis in this mutant and is consistent with a recent report demonstrating that GUN1 plays a role in tetrapyrrole metabolism by directly binding to tetrapyrroles such as Proto and by stimulating FC1 activity (Shimizu et al 2019). As such, by modulating tetrapyrrole synthesis or by sequestering Proto, GUN1 may play an indirect role in 1 O2 signaling from the chloroplast.…”

Overexpression of chloroplast-targeted ferrochelatase 1 results in a genomes uncoupled chloroplast-to-nucleus retrograde signalling phenotype

“…However, recently other roles have also been suggested in chloroplast RNA editing (Zhao et al, 2019) and import of nuclear-encoded chloroplast proteins (Wu et al, 2019). GUN1 has also been shown to interact with tetrapyrrole biosynthesis enzymes (Tadini et al, 2016), and to bind heme and a range of porphyrins and regulate FC1 enzyme activity in vitro (Shimizu et al, 2019). Given the strong evidence for a tetrapyrrole signal from the heme branch of the pathway, it could be proposed that GUN1 might have a role in co-ordinating various chloroplast processes with production of the FC1-dependent heme signal.…”

Retrograde signals from endosymbiotic organelles: a common control principle in eukaryotic cells

“…While GUN1, therefore, is strongly linked to various aspects of plastid protein synthesis, perhaps the most intriguing of the recent results on GUN1 is the observation that it can also alter tetrapyrrole metabolism [72]. The mechanism is not well understood but may involve interaction with tetrapyrrole enzymes [73] as well as direct tetrapyrrole-binding [72]. One possibility is that GUN1 provides a link between key chloroplast processes required for chloroplast protein synthesis and regulation of the tetrapyrrole pathway, where it may function to directly read out the FC1-dependent haem signal [72].…”