A major challenge for organic solar cell (OSC) research is how to minimize the tradeoff between voltage loss and charge generation. In early 2019, we reported a non-fullerene acceptor (named Y6) that can simultaneously achieve high external quantum efficiency and low voltage loss for OSC. Here, we use a combination of experimental and theoretical modeling to reveal the structure-property-performance relationships of this state-of-the-art OSC system. We find that the distinctive π–π molecular packing of Y6 not only exists in molecular single crystals but also in thin films. Importantly, such molecular packing leads to (i) the formation of delocalized and emissive excitons that enable small non-radiative voltage loss, and (ii) delocalization of electron wavefunctions at donor/acceptor interfaces that significantly reduces the Coulomb attraction between interfacial electron-hole pairs. These properties are critical in enabling highly efficient charge generation in OSC systems with negligible donor-acceptor energy offset.

Plants respond to phosphate (Pi) starvation by exhibiting a suite of developmental, biochemical, and physiological changes to cope with this nutritional stress. To understand the molecular mechanism underlying these responses, we isolated an Arabidopsis (Arabidopsis thaliana) mutant, hypersensitive to phosphate starvation1 (hps1), which has enhanced sensitivity in almost all aspects of plant responses to Pi starvation. Molecular and genetic analyses indicated that the mutant phenotype is caused by overexpression of the SUCROSE TRANSPORTER2 (SUC2) gene. As a consequence, hps1 has a high level of sucrose (Suc) in both its shoot and root tissues. Overexpression of SUC2 or its closely related family members SUC1 and SUC5 in wild-type plants recapitulates the phenotype of hps1. In contrast, the disruption of SUC2 functions greatly inhibits plant responses to Pi starvation. Microarray analysis further indicated that 73% of the genes that are induced by Pi starvation in wild-type plants can be induced by elevated levels of Suc in hps1 mutants, even when they are grown under Pi-sufficient conditions. These genes include several important Pi signaling components and those that are directly involved in Pi transport, mobilization, and distribution between shoot and root. Interestingly, Suc and low-Pi signals appear to interact with each other both synergistically and antagonistically in regulating gene expression. Our genetic and genomic studies provide compelling evidence that Suc is a global regulator of plant responses to Pi starvation. This finding will help to further elucidate the signaling mechanism that controls plant responses to this particular nutritional stress.

Summary With the exception of root hair development, the role of the phytohormone ethylene is not clear in other aspects of plant responses to inorganic phosphate (Pi) starvation. The induction of AtPT2 was used as a marker to find novel signalling components involved in plant responses to Pi starvation. Using genetic and chemical approaches, we examined the role of ethylene in the regulation of plant responses to Pi starvation. hps2, an Arabidopsis mutant with enhanced sensitivity to Pi starvation, was identified and found to be a new allele of CTR1 that is a key negative regulator of ethylene responses. 1‐aminocyclopropane‐1‐carboxylic acid (ACC), the precursor of ethylene, increases plant sensitivity to Pi starvation, whereas the ethylene perception inhibitor Ag+ suppresses this response. The Pi starvation‐induced gene expression and acid phosphatase activity are also enhanced in the hps2 mutant, but suppressed in the ethylene‐insensitive mutant ein2‐5. By contrast, we found that ethylene signalling plays a negative role in Pi starvation‐induced anthocyanin production. These findings extend the roles of ethylene in the regulation of plant responses to Pi starvation and will help us to gain a better understanding of the molecular mechanism underlying these responses.

Endoplasmic reticulum (ER)-associated degradation (ERAD) is an integral part of the ER quality-control system that removes toxic misfolded proteins via ubiquitin/proteasome-mediated degradation. Most of our knowledge on ERAD comes from biochemical and genetic studies in yeast and mammalian cells. Although ERAD is known to operate in plant cells, little is known about its molecular components and its biochemical mechanism. A genetic screen for suppressors of the Arabidopsis bri1-9, a weak dwarf mutant caused by ER retention of a structurally defective yet biochemically competent brassinosteroid (BR) receptor BRI1, resulted in identification of the EMS-mutagenized bri1 suppressor 5 (EBS5) gene that encodes an Arabidopsis homolog of the yeast Hrd3/mammlian Sel1L protein known to be involved in ERAD. Loss-of-function ebs5 mutations block the ERAD of bri1-9 and bri1-5, another ER-retained BR receptor. We showed that EBS5 complemented the ERAD defect of the yeast Δhrd3 mutant and interacted with the two mutated BR receptors in plant cells. Using a reverse genetic approach, we discovered that two Arabidopsis homologs of the yeast/mammalian Hrd1, an ER membrane-localized ubiquitin ligase, function redundantly in the ERAD of bri1-9. Together, our results revealed functional roles of two conserved ERAD components in degrading mutated/misfolded receptor-like kinases in Arabidopsis.plant steroid receptor | endoplasmic reticulum-associated degradation substrate-recruiting factor | E3 ligase | unfolded protein response

BackgroundMicroglial activation plays an important role in neurodegenerative diseases by producing several proinflammatory enzymes and proinflammatory cytokines. The phenolic glucoside gastrodin, a main constituent of a Chinese herbal medicine, has been known to display anti-inflammatory properties. The current study investigates the potential mechanisms whereby gastrodin affects the expression of potentially pro-inflammatory proteins by cultured murine microglial BV-2 cells stimulated with lipopolysaccharide (LPS).Methodology/Principal FindingsBV-2 cells were pretreated with gastrodin (30, 40, and 60 µM) for 1 h and then stimulated with LPS (1 µg/ml) for another 4 h. The effects on proinflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and proinflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), are analysed by double-immunofluorescence labeling and RT-PCR assay. To reveal the mechanisms of action of gastrodin we investigated the involvement of mitogen-activated protein kinases (MAPKs) cascades and their downstream transcription factors, nuclear factor-κB (NF-κB) and cyclic AMP-responsive element (CRE)-binding protein (CREB). Gastrodin significantly reduced the LPS-induced protein and mRNA expression levels of iNOS, COX-2, TNF-α, IL-1β and NF-κB. LPS (1 µg/ml, 30 min)-induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) and this was inhibited by pretreatment of BV-2 cells with different concentrations of gastrodin (30, 40, and 60 µM). In addition, gastrodin blocked LPS-induced phosphorylation of inhibitor κB-α (IκB-α) (and hence the activation of NF-κB) and of CREB, respectively.Conclusion and ImplicationsThis study indicates that gastrodin significantly attenuate levels of neurotoxic proinflammatory mediators and proinflammatory cytokines by inhibition of the NF-κB signaling pathway and phosphorylation of MAPKs in LPS-stimulated microglial cells. Arising from the above, we suggest that gastrodin has a potential as an anti-inflammatory drug candidate in neurodegenerative diseases.

A correct three-dimensional structure is crucial for the physiological functions of a protein, yet the folding of proteins to acquire native conformation is a fundamentally error-prone process. Eukaryotic organisms have evolved a highly conserved endoplasmic reticulum-mediated protein quality control (ERQC) mechanism to monitor folding processes of secretory and membrane proteins, allowing export of only correctly folded proteins to their physiological destinations, retaining incompletely/mis-folded ones in the ER for additional folding attempts, marking and removing terminally misfolded ones via a unique multiple-step degradation process known as ER-associated degradation (ERAD). Most of our current knowledge on ERQC and ERAD came from genetic and biochemical investigations in yeast and mammalian cells. Recent studies in the reference plant Arabidopsis thaliana uncovered homologous components and similar mechanisms in plants for monitoring protein folding and for retaining, repairing, and removing misfolded proteins. These studies also revealed critical roles of the plant ERQC/ERAD systems in regulating important biochemical/physiological processes, such as abiotic stress tolerance and plant defense. In this review, we discuss our current understanding about the molecular components and biochemical mechanisms of the plant ERQC/ERAD system in comparison to yeast and mammalian systems.

The endoplasmic reticulum-associated degradation (ERAD) is a highly conserved mechanism to remove misfolded membrane/secretory proteins from the endoplasmic reticulum (ER). While many of the individual components of the ERAD machinery are well characterized in yeast and mammals, our knowledge of a plant ERAD process is rather limited. Here, we report a functional study of an Arabidopsis homolog (AtOS9) of an ER luminal lectin Yos9 (OS-9 in mammals) that recognizes a unique asparagine-linked glycan on misfolded proteins. We discovered that AtOS9 is an ER-localized glycoprotein that is co-expressed with many known/predicted ER chaperones. A T-DNA insertional atos9-t mutation blocks the degradation of a structurally imperfect yet biochemically competent brassinosteroid (BR) receptor bri1-9, causing its increased accumulation in the ER and its consequent leakage to the cell surface responsible for restoring the BR sensitivity and suppressing the dwarfism of the bri1-9 mutant. In addition, we identified a missense mutation in AtOS9 in a recently discovered ERAD mutant ems-mutagenized bri1 suppressor 6 (ebs6-1). Moreover, we showed that atos9-t also inhibits the ERAD of bri1-5, another ER-retained BR receptor, and a misfolded EFR, a BRI1-like receptor for the bacterial translation elongation factor EF-Tu. Furthermore, we found that AtOS9 interacted biochemically and genetically with EBS5, an Arabidopsis homolog of the yeast Hrd3/mammalian Sel1L known to collaborate with Yos9/OS-9 to select ERAD clients. Taken together, our results demonstrated a functional role of AtOS9 in a plant ERAD process that degrades misfolded receptor-like kinases.

Endoplasmic reticulum (ER)-associated degradation (ERAD) is an essential part of an ER-localized protein quality-control system for eliminating terminally misfolded proteins. Recent studies have demonstrated that the ERAD machinery is conserved among yeast, animals, and plants; however, it remains unknown if the plant ERAD system involves plant-specific components. Here we report that the Arabidopsis ethyl methanesulfonate-mutagenized brassinosteroidinsensitive 1 suppressor 7 (EBS7) gene encodes an ER membranelocalized ERAD component that is highly conserved in land plants. Loss-of-function ebs7 mutations prevent ERAD of brassinosteroid insensitive 1-9 (bri1-9) and bri1-5, two ER-retained mutant variants of the cell-surface receptor for brassinosteroids (BRs). As a result, the two mutant receptors accumulate in the ER and consequently leak to the plasma membrane, resulting in the restoration of BR sensitivity and phenotypic suppression of the bri1-9 and bri1-5 mutants. EBS7 accumulates under ER stress, and its mutations lead to hypersensitivity to ER and salt stresses. EBS7 interacts with the ER membrane-anchored ubiquitin ligase Arabidopsis thaliana HMGCoA reductase degradation 1a (AtHrd1a), one of the central components of the Arabidopsis ERAD machinery, and an ebs7 mutation destabilizes AtHrd1a to reduce polyubiquitination of bri1-9. Taken together, our results uncover a plant-specific component of a plant ERAD pathway and also suggest its likely biochemical function.is an integral part of an ER-mediated protein quality-control system in eukaryotes, which permits export of only correctly folded proteins but retains misfolded proteins in the ER for repair via additional folding attempts or removal through ERAD. Genetic and biochemical studies in yeast and mammalian cells have revealed that the core ERAD machinery is highly conserved between yeast and mammals and that ERAD involves four tightly coupled steps: substrate selection, retrotranslocation through the ER membrane, ubiquitination, and proteasome-mediated degradation (1, 2).Because the great majority of secretory/membrane proteins are glycosylated in the ER, diversion of most ERAD substrates from their futile folding cycles into ERAD is initiated through progressive mannose trimming of their asparagine-linked glycans (N-glycans) by ER/Golgi-localized class I mannosidases, including homologous to α-mannosidase 1 (Htm1) and its mammalian homologs ER degradation-enhancing α-mannosidase-like proteins (EDEMs) (3). The processed glycoproteins are captured by two ER resident proteins, yeast amplified in osteosarcoma 9 (OS9 in mammals) homolog (Yos9) and HMG-CoA reductase degradation 3 (Hrd3) [suppressor/enhancer of Lin-12-like (SEL1L) in mammals], which recognize the mannose-trimmed N-glycans and surface-exposed hydrophobic amino acid residues, respectively (4, 5). The selected ERAD clients are delivered to an ER membraneanchored ubiquitin ligase (E3), which is the core component of the ERAD machinery (6), for polyubiquitination. Yeast has two known ERAD E3 lig...