Review: Endoplasmic Reticulum-Associated Degradation (ERAD)-Dependent Control of (Tri)terpenoid Metabolism in Plants

Abstract

Plants are sessile organisms. Therefore, they developed the capacity to quickly respond to biotic and abiotic environmental stresses, for instance by producing a broad spectrum of bioactive specialized metabolites. In this defense response, the jasmonate phytohormones can instigate a signaling cascade that leads to the specific elicitation and reprograming of numerous metabolic pathways. Recent research progress has provided several insights into the regulatory networks of many specialized metabolic pathways, mainly at the transcriptional level. Nonetheless, our view on the regulation of defense metabolism remains far from comprehensive. Here, we describe the recent advances obtained with regard to one aspect of the regulation of plant specialized metabolism, namely the posttranslational regulation of enzyme stability. We focus on terpenoid biosynthesis and in particular on the rate-limiting and well-investigated enzyme of the terpenoid precursor pathway, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR). There are clear similarities, as well as important mechanistic differences, among the components involved in the posttranslational regulation of terpenoid biosynthesis via HMGR in plants, yeasts, and mammals. Furthermore, in plants, several of these components evolved to respond to specific signaling cues. Indeed, the elements of the plant endoplasmic reticulum-associated degradation (ERAD) and ER stress-associated processes can be induced upon environmental stresses and during specific developmental processes, thereby allowing a unique posttranslational regulation of terpenoid biosynthesis pathways.

HIGH STEROL ESTER 1 is a key factor in plant sterol homeostasis

“…In yeast and animals, regulatory factors including E3 ubiquitin ligases function in the ERAD of HMGR proteins 21 . In plants, the E3 ubiquitin ligase MAKIBISHI1 mediates the ERAD of HMGR proteins in Medicago truncatula 12 .…”

“…ERAD is also involved in regulating HMGR at the protein level in Medicago truncatula 12 and at the activity level in A. thaliana 20 . In addition to the similar regulations to those of yeast and animals, plants have the potential to evolve a unique regulation 21 . However, plant-specific mechanism underlying sterol biosynthesis is not known.…”

Biosynthesis and the Roles of Plant Sterols in Development and Stress Responses

“…Research about the post-transcriptional regulation of sterols is mainly focused on hydroxymethylglutaryl-CoA reductase (HMGR), a rate-limiting enzyme in the plant sterols biosynthetic pathway [143]. In the past, the post-translational regulation of HMGR included phosphorylation, glycosylation, ubiquitin, and protein degradation [144][145][146]. Recently, a new negative regulator HIGH STEROL ESTER1 (HISE1) was found in A. thaliana, which can significantly reduce protein activity of HMGR1 and HMGR2, thus inhibiting the overproduction of sterols.…”

ER-Phagy: A New Regulator of ER Homeostasis

“…ERAD not only is a process dedicated to ER protein quality control but also controls the turnover of specific proteins to achieve certain physiological states (Ruggiano et al, 2014). ERAD regulates the cellular contents of some key proteins involved in lipid biosynthesis and calcium homeostasis, such as 3-hydroxy-3-methyl-glutaryl acetyl coenzyme-A reductase (HMGR), a rate-limiting enzyme involved in the synthesis of cholesterol (Erffelinck and Goossens, 2018;Wangeline and Hampton, 2018). The degradation of HMGR by ERAD results in reduced flux through the sterol biosynthetic pathway and in the reestablishment of membrane lipid homeostasis (Fernandez et al, 2015).…”