BACKGROUND: Congenital disorders of glycosylation (CDG) are inherited metabolic diseases caused by defects in the genes important for the process of protein and lipid glycosylation. With the ever growing number of the known subtypes and discoveries regarding the disease mechanisms and therapy development, it remains a very active field of study. SCOPE OF REVIEW: This review brings an update on the CDG-related research since 2017, describing the novel gene defects, pathobiomechanisms, biomarkers and the patients' phenotypes. We also summarize the clinical guidelines for the most prevalent disorders and the current therapeutical options for the treatable CDG. MAJOR CONCLUSIONS: In the majority of the 23 new CDG, neurological involvement is associated with other organ disease. Increasingly, different aspects of cellular metabolism (e.g., autophagy) are found to be perturbed in multiple CDG. GENERAL SIGNIFICANCE: This work highlights the recent trends in the CDG field and comprehensively overviews the up-to-date clinical recommendations.
- MeSH
- glykosylace MeSH
- lidé MeSH
- lipidy genetika MeSH
- metabolické sítě a dráhy MeSH
- metabolismus lipidů MeSH
- mutace MeSH
- proteiny genetika metabolismus MeSH
- vrozené poruchy glykosylace genetika metabolismus patologie terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
In Part I, by using 31P-NMR spectroscopy, we have shown that isolated granum and stroma thylakoid membranes (TMs), in addition to the bilayer, display two isotropic phases and an inverted hexagonal (HII) phase; saturation transfer experiments and selective effects of lipase and thermal treatments have shown that these phases arise from distinct, yet interconnectable structural entities. To obtain information on the functional roles and origin of the different lipid phases, here we performed spectroscopic measurements and inspected the ultrastructure of these TM fragments. Circular dichroism, 77 K fluorescence emission spectroscopy, and variable chlorophyll-a fluorescence measurements revealed only minor lipase- or thermally induced changes in the photosynthetic machinery. Electrochromic absorbance transients showed that the TM fragments were re-sealed, and the vesicles largely retained their impermeabilities after lipase treatments-in line with the low susceptibility of the bilayer against the same treatment, as reflected by our 31P-NMR spectroscopy. Signatures of HII-phase could not be discerned with small-angle X-ray scattering-but traces of HII structures, without long-range order, were found by freeze-fracture electron microscopy (FF-EM) and cryo-electron tomography (CET). EM and CET images also revealed the presence of small vesicles and fusion of membrane particles, which might account for one of the isotropic phases. Interaction of VDE (violaxanthin de-epoxidase, detected by Western blot technique in both membrane fragments) with TM lipids might account for the other isotropic phase. In general, non-bilayer lipids are proposed to play role in the self-assembly of the highly organized yet dynamic TM network in chloroplasts.
DivIVA is a crucial membrane-binding protein that helps to localize other proteins to negatively curved membranes at cellular poles and division septa in Gram-positive bacteria. The N-terminal domain of DivIVA is responsible for membrane binding. However, to which lipids the domain binds or how it recognizes the membrane negative curvature remains elusive. Using computer simulations, we demonstrate that the N-terminal domain of Streptomyces coelicolor DivIVA adsorbs to membranes with affinity and orientation dependent on the lipid composition. The domain interacts non-specifically with lipid phosphates via its arginine-rich tip and the strongest interaction is with cardiolipin. Moreover, we observed a specific attraction between a negatively charged side patch of the domain and ethanolamine lipids, which addition caused the change of the domain orientation from perpendicular to parallel alignment to the membrane plane. Similar but less electrostatically dependent behavior was observed for the N-terminal domain of Bacillus subtilis. The domain propensity for lipids which prefer negatively curved membranes could be a mechanism for the cellular localization of DivIVA protein.
- MeSH
- Bacillus subtilis genetika MeSH
- bakteriální proteiny genetika MeSH
- lipidy genetika MeSH
- membránové proteiny genetika MeSH
- proteinové domény genetika MeSH
- proteiny buněčného cyklu genetika MeSH
- Streptomyces coelicolor genetika MeSH
- vazba proteinů genetika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
We present Mass Spectrometry-Data Independent Analysis software version 4 (MS-DIAL 4), a comprehensive lipidome atlas with retention time, collision cross-section and tandem mass spectrometry information. We formulated mass spectral fragmentations of lipids across 117 lipid subclasses and included ion mobility tandem mass spectrometry. Using human, murine, algal and plant biological samples, we annotated and semiquantified 8,051 lipids using MS-DIAL 4 with a 1-2% estimated false discovery rate. MS-DIAL 4 helps standardize lipidomics data and discover lipid pathways.
The endodermis is a key cell layer in plant roots that contributes to the controlled uptake of water and mineral nutrients into plants. In order to provide such functionality the endodermal cell wall has specific chemical modifications consisting of lignin bands (Casparian strips) that encircle each cell, and deposition of a waxy-like substance (suberin) between the wall and the plasma membrane. These two extracellular deposits provide control of diffusion enabling the endodermis to direct the movement of water and solutes into and out of the vascular system in roots. Loss of integrity of the Casparian strip-based apoplastic barrier is sensed by the leakage of a small peptide from the stele into the cortex. Here, we report that such sensing of barrier integrity leads to the rebalancing of water and mineral nutrient uptake, compensating for breakage of Casparian strips. This rebalancing involves both a reduction in root hydraulic conductivity driven by deactivation of aquaporins, and downstream limitation of ion leakage through deposition of suberin. These responses in the root are also coupled to a reduction in water demand in the shoot mediated by ABA-dependent stomatal closure.
- MeSH
- Arabidopsis genetika metabolismus MeSH
- biologický transport fyziologie MeSH
- buněčná stěna genetika metabolismus MeSH
- difuze MeSH
- kořeny rostlin genetika metabolismus MeSH
- lignin genetika metabolismus MeSH
- lipidy genetika MeSH
- voda metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Abscisic acid (ABA) is a key phytohormone underlying plant resistance to toxic metals. However, regulatory effects of ABA on apoplastic transport in roots and consequences for uptake of metal ions are poorly understood. Here, we demonstrate how ABA regulates development of apoplastic barriers in roots of two ecotypes of Sedum alfredii and assess effects on cadmium (Cd) uptake. Under Cd treatment, increased endogenous ABA level was detected in roots of nonhyperaccumulating ecotype (NHE) due to up-regulated expressions of ABA biosynthesis genes (SaABA2, SaNCED), but no change was observed in hyperaccumulating ecotype (HE). Simultaneously, endodermal Casparian strips (CSs) and suberin lamellae (SL) were deposited closer to root tips of NHE compared with HE. Interestingly, the vessel-to-CSs overlap was identified as an ABA-driven anatomical trait. Results of correlation analyses and exogenous applications of ABA/Abamine indicate that ABA regulates development of both types of apoplastic barriers through promoting activities of phenylalanine ammonialyase, peroxidase, and expressions of suberin-related genes (SaCYP86A1, SaGPAT5, and SaKCS20). Using scanning ion-selected electrode technique and PTS tracer confirmed that ABA-promoted deposition of CSs and SL significantly reduced Cd entrance into root stele. Therefore, maintenance of low ABA levels in HE minimized deposition of apoplastic barriers and allowed maximization of Cd uptake via apoplastic pathway.
- MeSH
- biologický transport genetika fyziologie MeSH
- kadmium metabolismus MeSH
- kořeny rostlin anatomie a histologie metabolismus MeSH
- kyselina abscisová metabolismus MeSH
- lipidy genetika MeSH
- regulace genové exprese u rostlin MeSH
- regulátory růstu rostlin genetika metabolismus MeSH
- Sedum genetika metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- apolipoproteiny E genetika MeSH
- celogenomová asociační studie MeSH
- dědičnost * fyziologie genetika MeSH
- DNA genetika chemie MeSH
- dyslipidemie * genetika klasifikace patologie genetika patologie MeSH
- epigenomika MeSH
- gen pro FTO MeSH
- genetická predispozice k nemoci * MeSH
- geny genetika MeSH
- hypercholesterolemie genetika patologie MeSH
- index tělesné hmotnosti MeSH
- interakce genů a prostředí MeSH
- LDL-cholesterol MeSH
- lidé MeSH
- lipidy genetika klasifikace krev MeSH
- mutace MeSH
- obezita * etiologie genetika patologie MeSH
- polymorfismus genetický MeSH
- terminologie jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Lipids are among the most important organic compounds found in all living cells, from primitive archaebacteria to flowering plants or mammalian cells. They form part of cell walls and constitute cell storage material. Their biosynthesis and metabolism play key roles in faraway topics such as biofuel production (third-generation biofuels produced by microorganisms, e.g. algae) and human diseases such as adrenoleukodystrophy, Zellweger syndrome, or Refsum disease. Current lipidomic analysis requires fast and accurate processing of samples and especially their characterization. Because the number of possible lipids and, more specifically, molecular species of lipids is of the order of hundreds to thousands, it is necessary to process huge amounts of data in a short time. There are two basic approaches to lipidomic analysis: shotgun and liquid chromatography-mass spectometry. Both methods have their pros and cons. This review deals with lipidomics not according to the type of ionization or the lipid classes analyzed but according to the types of samples (organisms) under study. Thus, it is divided into lipidomic analysis of archaebacteria, bacteria, yeast, fungi, algae, plants, and animals.
- MeSH
- Archaea chemie genetika MeSH
- chromatografie kapalinová MeSH
- lidé MeSH
- lipidy chemie genetika MeSH
- metabolismus lipidů genetika MeSH
- metabolomika metody MeSH
- savci genetika MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Although the significance of apoplasmic barriers in roots with regards to the uptake of toxic elements is generally known, the contribution of apoplasmic bypasses (ABs) to cadmium (Cd) hyperaccumulation is little understood. Here, we employed a combination of stable isotopic tracer techniques, an ABs tracer, hydraulic measurements, suberin lamellae staining, metabolic inhibitors, and antitranspirants to investigate and quantify the impact of the ABs on translocation of Cd to the xylem in roots of a hyperaccumulating (H) ecotype and a non-hyperaccumulating (NH) ecotype of Sedum alfredii. In the H ecotype, the Cd content in the xylem sap was proportional to hydrostatic pressure, which was attributed to pressure-driven flow via the ABs. The contribution of the ABs to Cd transportation to the xylem was dependent on the Cd concentration applied to the H ecotype (up to 37% at the highest concentration used). Cd-treated H ecotype roots showed significantly higher hydraulic conductance compared with the NH ecotype (76 vs 52 × 10–8 m s–1MPa–1), which is in accordance with less extensive suberization due to reduced expression of suberin-related genes. The main entry sites of apoplasmically transported Cd were localized in the root apexes and lateral roots of the H ecotype, where suberin lamellae were not well developed. These findings highlight the significance of the apoplasmic bypass in Cd hyperaccumulation in hyperaccumulating ecotypes of S. alfredii.
Recently, genome-wide genetic screening of common DNA sequence variants has proven a successful approach to identify novel genetic contributors to complex traits. This review summarizes recent genome-wide association studies for lipid phenotypes, and evaluates the next steps needed to obtain a full picture of genotype-phenotype correlation and apply these findings to inform clinical practice. RECENT FINDINGS: So far, genome-wide association studies have defined at least 19 genomic regions that contain common DNA single nucleotide polymorphisms associated with LDL cholesterol, HDL cholesterol and/or triglycerides. Of these, eight represent novel loci in humans, whereas 11 genes have been previously implicated in lipoprotein metabolism. Many of the same loci with common variants have already been shown to lead to monogenic lipid disorders in humans and/or mice, suggesting that a spectrum of common and rare alleles at each validated locus contributes to blood lipid concentrations. SUMMARY: At least 19 loci harbor common variations that contribute to blood lipid concentrations in humans. Larger scale genome-wide association studies should identify additional loci, and sequencing of these loci should pinpoint all relevant alleles. With a full catalog of DNA polymorphisms in hand, a panel of lipid-related variants can be studied to provide clinical risk stratification and targeting of therapeutic interventions.
