scholarly journals The oncometabolite L-2-hydroxyglutarate is a common product of Dipteran larval development

2020 ◽  
Author(s):  
Nader H. Mahmoudzadeh ◽  
Alexander J. Fitt ◽  
Daniel B. Schwab ◽  
William E. Martenis ◽  
Lauren M. Nease ◽  
...  

ABSTRACTThe oncometabolite L-2-hydroxyglutarate (L-2HG) is considered an abnormal product of central carbon metabolism that is capable of disrupting chromatin architecture, mitochondrial metabolism, and cellular differentiation. Under most circumstances, mammalian tissues readily dispose of this compound, as aberrant L-2HG accumulation induces neurometabolic disorders and promotes renal cell carcinomas. Intriguingly, Drosophila melanogaster larvae were recently found to accumulate high L-2HG levels under normal growth conditions, raising the possibility that L-2HG plays a unique role in insect metabolism. Here we explore this hypothesis by analyzing L-2HG levels in 18 insect species. While L-2HG was present at low-to-moderate levels in most of these species (<100 pmol/mg; comparable to mouse liver), Dipteran larvae exhibited a tendency to accumulate high L-2HG concentrations (>100 pmol/mg), with the mosquito Aedes aegypti, the blow fly Phormia regina, and three representative Drosophila species harboring concentrations that exceed 1 nmol/mg – levels comparable to those measured in mutant mice that are unable to degrade L-2HG. Overall, our findings suggest that one of the largest groups of animals on earth commonly generate high concentrations of an oncometabolite during juvenile growth, hint at a role for L-2HG in the evolution of Dipteran development, and raise the possibility that L-2HG metabolism could be targeted to restrict the growth of key disease vectors and agricultural pests.

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 697
Author(s):  
Juan Mao ◽  
Wenxin Li ◽  
Jing Liu ◽  
Jianming Li

The plant glycogen synthase kinase 3 (GSK3)-like kinases are highly conserved protein serine/threonine kinases that are grouped into four subfamilies. Similar to their mammalian homologs, these kinases are constitutively active under normal growth conditions but become inactivated in response to diverse developmental and environmental signals. Since their initial discoveries in the early 1990s, many biochemical and genetic studies were performed to investigate their physiological functions in various plant species. These studies have demonstrated that the plant GSK3-like kinases are multifunctional kinases involved not only in a wide variety of plant growth and developmental processes but also in diverse plant stress responses. Here we summarize our current understanding of the versatile physiological functions of the plant GSK3-like kinases along with their confirmed and potential substrates.


Genetics ◽  
2001 ◽  
Vol 157 (1) ◽  
pp. 211-224 ◽  
Author(s):  
Joseph H Chou ◽  
Cornelia I Bargmann ◽  
Piali Sengupta

Abstract Caenorhabditis elegans odr-2 mutants are defective in the ability to chemotax to odorants that are recognized by the two AWC olfactory neurons. Like many other olfactory mutants, they retain responses to high concentrations of AWC-sensed odors; we show here that these residual responses are caused by the ability of other olfactory neurons (the AWA neurons) to be recruited at high odor concentrations. odr-2 encodes a membrane-associated protein related to the Ly-6 superfamily of GPI-linked signaling proteins and is the founding member of a C. elegans gene family with at least seven other members. Alternative splicing of odr-2 yields three predicted proteins that differ only at the extreme amino terminus. The three isoforms have different promoters, and one isoform may have a unique role in olfaction. An epitope-tagged ODR-2 protein is expressed at high levels in sensory neurons, motor neurons, and interneurons and is enriched in axons. The AWC neurons are superficially normal in their development and structure in odr-2 mutants, but their function is impaired. Our results suggest that ODR-2 may regulate AWC signaling within the neuronal network required for chemotaxis.


Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1009
Author(s):  
Kirill Tkachenko ◽  
Irina Kosareva ◽  
Marina Frontasyeva

Manganese, as one of the xenobionts, belongs to the group of heavy metals, which, in high concentrations, can negatively affect the development of plants. In small concentrations, it is necessary for plants for normal growth and development. It is present in soils and is available to plants to varying degrees. In acidic soils, it often acts as a toxic element, and plants do not develop well and can even die. Screening major crops for manganese tolerance is essential. Based on the analysis of the collection of barley (Hordeum L., Poaceae), the N.I. Vavilov All-Russian Institute of Plant Genetic Resources (VIR) presented data that manganese-tolerant varieties and samples are concentrated in western and northern countries with a wide distribution of soils with low pH levels and high contents of mobile manganese. It follows from the diagnostic results that the maximum number of barley genotypes resistant to manganese is concentrated in Sweden, Finland, the northwestern and northern regions of the CIS countries, and the Russian Federation. In most cases, the samples tolerant to Al showed resistance to Mn as well, which is of great interest for further study of the mechanisms of plant resistance to these stressors. As a rule, samples from the northern territories—zones of distribution of acidic soils—were highly resistant. In this case, the role of the species belonging to the sample was leveled out. The highlighted areas (Scandinavia (Finland, Sweden), northern and northwestern regions of Russia, Belarus, and the Baltic countries) are sources of germplasm valuable for selection for acid resistance of barley.


1989 ◽  
Vol 9 (6) ◽  
pp. 2615-2626 ◽  
Author(s):  
E Hickey ◽  
S E Brandon ◽  
G Smale ◽  
D Lloyd ◽  
L A Weber

Vertebrate cells synthesize two forms of the 82- to 90-kilodalton heat shock protein that are encoded by distinct gene families. In HeLa cells, both proteins (hsp89 alpha and hsp89 beta) are abundant under normal growth conditions and are synthesized at increased rates in response to heat stress. Only the larger form, hsp89 alpha, is induced by the adenovirus E1A gene product (M. C. Simon, K. Kitchener, H. T. Kao, E. Hickey, L. Weber, R. Voellmy, N. Heintz, and J. R. Nevins, Mol. Cell. Biol. 7:2884-2890, 1987). We have isolated a human hsp89 alpha gene that shows complete sequence identity with heat- and E1A-inducible cDNA used as a hybridization probe. The 5'-flanking region contained overlapping and inverted consensus heat shock control elements that can confer heat-inducible expression on a beta-globin reporter gene. The gene contained 10 intervening sequences. The first intron was located adjacent to the translation start codon, an arrangement also found in the Drosophila hsp82 gene. The spliced mRNA sequence contained a single open reading frame encoding an 84,564-dalton polypeptide showing high homology with the hsp82 to hsp90 proteins of other organisms. The deduced hsp89 alpha protein sequence differed from the human hsp89 beta sequence reported elsewhere (N. F. Rebbe, J. Ware, R. M. Bertina, P. Modrich, and D. W. Stafford (Gene 53:235-245, 1987) in at least 99 out of the 732 amino acids. Transcription of the hsp89 alpha gene was induced by serum during normal cell growth, but expression did not appear to be restricted to a particular stage of the cell cycle. hsp89 alpha mRNA was considerably more stable than the mRNA encoding hsp70, which can account for the higher constitutive rate of hsp89 synthesis in unstressed cells.


1988 ◽  
Vol 8 (9) ◽  
pp. 3827-3836
Author(s):  
N P Williams ◽  
P P Mueller ◽  
A G Hinnebusch

Translational control of GCN4 expression in the yeast Saccharomyces cerevisiae is mediated by multiple AUG codons present in the leader of GCN4 mRNA, each of which initiates a short open reading frame of only two or three codons. Upstream AUG codons 3 and 4 are required to repress GCN4 expression in normal growth conditions; AUG codons 1 and 2 are needed to overcome this repression in amino acid starvation conditions. We show that the regulatory function of AUG codons 1 and 2 can be qualitatively mimicked by the AUG codons of two heterologous upstream open reading frames (URFs) containing the initiation regions of the yeast genes PGK and TRP1. These AUG codons inhibit GCN4 expression when present singly in the mRNA leader; however, they stimulate GCN4 expression in derepressing conditions when inserted upstream from AUG codons 3 and 4. This finding supports the idea that AUG codons 1 and 2 function in the control mechanism as translation initiation sites and further suggests that suppression of the inhibitory effects of AUG codons 3 and 4 is a general consequence of the translation of URF 1 and 2 sequences upstream. Several observations suggest that AUG codons 3 and 4 are efficient initiation sites; however, these sequences do not act as positive regulatory elements when placed upstream from URF 1. This result suggests that efficient translation is only one of the important properties of the 5' proximal URFs in GCN4 mRNA. We propose that a second property is the ability to permit reinitiation following termination of translation and that URF 1 is optimized for this regulatory function.


2012 ◽  
Vol 60 (1) ◽  
pp. 1-10 ◽  
Author(s):  
D. Todorova ◽  
I. Sergiev ◽  
V. Alexieva

Wheat cultivars were grown as soil culture under normal growth conditions. Twoweek- old seedlings were exposed to 4°C for 6 h and then transferred to −12°C for 24 h in the dark. Twenty-four hours before freezing stress, some of the plants were sprayed with aqueous solutions of spermine, spermidine, putrescine, 1,3-diaminopropane (1,3-DAP) and diethylenetriamine (DETA). The data showed that freezing stress caused a decrease in the fresh weight, chlorophyll content and plant survival rate, accompanied by a simultaneous accumulation of free proline and the enhanced leakage of electrolytes. Preliminary treatment with polyamines caused a decline in electrolyte leakage and a considerable augmentation in proline quantity, indicating that the compounds are capable of preventing frost injury. Additionally, the foliar application of polyamines retarded the destruction of chlorophyll, and lessened fresh weight losses due to freezing stress. The synthetic triamine DETA was the most effective, having the most pronounced action in all the experiments, followed by the tetraamine spermine. The application of polyamines to wheat crops could be a promising approach for improving plant growth under unfavourable growth conditions, including freezing temperatures. The results demonstrate that treatment with polyamines could protect winter wheat by reducing the stress injuries caused by subzero temperatures.


Genetics ◽  
1988 ◽  
Vol 119 (2) ◽  
pp. 457-464
Author(s):  
Y B Pan ◽  
P A Peterson

Abstract This study addresses the question of the activation of quiescent transposable elements in maize breeding lines. The a-ruq reporter allele of the Uq transposable element system expresses Uq activity (spots or sectors of spots in otherwise colorless aleurone tissue) when exposed to various genotypes of assorted maize inbred lines lacking any active Uq element. This activation of quiescent Uq elements occurs randomly during the growth of the endosperm. It is concluded that there are components in the genome that enhance the rare activation of quiescent Uq elements. Further, it seems that this activation occurs in the absence of any stress-inducing treatment, but that normal growth conditions provide sufficient stimulus for such activation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jiahong Zhu ◽  
Wan Zhao ◽  
Rongshuang Li ◽  
Dong Guo ◽  
Huiliang Li ◽  
...  

Dragon’s blood is a traditional medicine in which flavonoids are the main bioactive compounds; however, the underlying formation mechanism of dragon’s blood remains largely poorly understood. Chalcone isomerase (CHI) is the key enzyme in the flavonoid biosynthesis pathway. However, CHI family genes are not well understood in Dracaena cambodiana Pierre ex Gagnep, an important source plant of dragon’s blood. In this study, 11 CHI family genes were identified from D. cambodiana, and they were classified into three types. Evolutionary and transcriptional profiling analysis revealed that DcCHI1 and DcCHI4 might be involved in flavonoid production. Both DcCHI1 and DcCHI4 displayed low expression levels in stem under normal growth conditions and were induced by methyl jasmonate (MeJA), 6-benzyl aminopurine (6-BA, synthetic cytokinin), ultraviolet-B (UV-B), and wounding. The recombinant proteins DcCHI1 and DcCHI4 were expressed in Escherichia coli and purified by His-Bind resin chromatography. Enzyme activity assay indicated that DcCHI1 catalyzed the formation of naringenin from naringenin chalcone, while DcCHI4 lacked this catalytic activity. Overexpression of DcCHI1 or DcCHI4 enhanced the flavonoid production in D. cambodiana and tobacco. These findings implied that DcCHI1 and DcCHI4 play important roles in flavonoid production. Thus, our study will not only contribute to better understand the function and expression regulation of CHI family genes involved in flavonoid production in D. cambodiana but also lay the foundation for developing the effective inducer of dragon’s blood.


2021 ◽  
Author(s):  
Jianhui Li ◽  
Mark Hochstrasser

The proteasome is central to proteolysis by the ubiquitin-proteasome system under normal growth conditions but is itself degraded through macroautophagy under nutrient stress. A recently described AMPK (AMP-activated protein kinase)-regulated ESCRT (endosomal sorting complex required for transport)-dependent microautophagy pathway also regulates proteasome trafficking and degradation in low glucose conditions in yeast. Aberrant proteasomes are more prone to microautophagy, suggesting the ESCRT system fine-tunes proteasome quality control under low glucose stress. Here we uncover additional features of the selective microautophagy of proteasomes. Genetic or pharmacological induction of aberrant proteasomes is associated with increased mono- or oligo-ubiquitylation of proteasome components, which appear to be recognized by ESCRT-0. AMPK controls this pathway in part by regulating the trafficking of ESCRT-0 to the vacuole surface, which also leads to degradation of the Vps27 subunit of ESCRT-0. The Rsp5 ubiquitin ligase contributes to proteasome subunit ubiquitylation, and multiple ubiquitin-binding elements in Vps27 are involved in their recognition. We propose that ESCRT-0 at the vacuole surface recognizes ubiquitylated proteasomes and initiates their microautophagic elimination during glucose depletion.


2021 ◽  
Vol 22 (22) ◽  
pp. 12583
Author(s):  
Qingsong Gao ◽  
Lei Liu ◽  
Haiying Zhou ◽  
Xi Liu ◽  
Wei Li ◽  
...  

Micronutrient metals, such as Mn, Cu, Fe, and Zn, are essential heavy metals for plant growth and development, while Cd is a nonessential heavy metal that is highly toxic to both plants and humans. Our understanding of the molecular mechanisms underlying Cd and micronutrient metal accumulation in plants remains incomplete. Here, we show that OsFWL7, an FW2.2-like (FWL) family gene in Oryza sativa, is preferentially expressed in the root and encodes a protein localized to the cell membrane. The osfwl7 mutation reduces both the uptake and the root-to-shoot translocation of Cd in rice plants. Additionally, the accumulation of micronutrient metals, including Mn, Cu, and Fe, was lower in osfwl7 mutants than in the wildtype plants under normal growth conditions. Moreover, the osfwl7 mutation affects the expression of several heavy metal transporter genes. Protein interaction analyses reveal that rice FWL proteins interact with themselves and one another, and with several membrane microdomain marker proteins. Our results suggest that OsFWL7 is involved in Cd and micronutrient metal accumulation in rice. Additionally, rice FWL proteins may form oligomers and some of them may be located in membrane microdomains.


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