Ether lipids, such as plasmalogens, are peroxisome- derived glycerophospholipids in which the hydrocarbon chain at the sn-1 position of the glycerol backbone is attached by an ether bond, as opposed ...to an ester bond in the more common diacyl phospholipids. This seem- ingly simple biochemical change has profound structural and functional implications. Notably, the tendency of ether lipids to form non-lamellar inverted hexagonal structures in model membranes suggests that they have a role in facilitating membrane fusion processes. Ether lipids are also important for the organization and stability of lipid raft microdomains, cholesterol-rich membrane regions involved in cellular signaling. In addition to their structural roles, a subset of ether lipids are thought to function as endogenous antioxidants, and emerging studies suggest that they are involved in cell differentiation and signaling pathways. Here, we review the biology of ether lipids and their potential signifi- cance in human disorders, including neurological diseases, cancer, and metabolic disorders.
Peroxisomes are involved in multiple metabolic processes, including fatty acid oxidation, ether lipid synthesis, and reactive oxygen species (ROS) metabolism. Recent studies suggest that peroxisomes ...are critical mediators of cellular responses to various forms of stress, including oxidative stress, hypoxia, starvation, cold exposure, and noise. As dynamic organelles, peroxisomes can modulate their proliferation, morphology, and movement within cells, and engage in crosstalk with other organelles in response to external cues. Although peroxisome-derived hydrogen peroxide has a key role in cellular signaling related to stress, emerging studies suggest that other products of peroxisomal metabolism, such as acetyl-CoA and ether lipids, are also important for metabolic adaptation to stress. Here, we review molecular mechanisms through which peroxisomes regulate metabolic and environmental stress.
Peroxisomes are not only passive performers of various metabolic reactions, but also a critical signaling hub that integrates signals originating from these reactions and communicates with other organelles to respond to various stressors, including oxidative stress, hypoxia, starvation, cold, noise, and pathogens.Although peroxisome-derived ROS has a key role in cellular signaling related to stress, recent studies suggest that other products of peroxisomal metabolism, such as acetyl-CoA and ether lipids, are also important for metabolic adaptation to stress.Peroxisomes control lipid hydrolysis and mobilization during nutrient deprivation through their ability to engage in crosstalk with other organelles and to generate signaling metabolites, such as acetyl-CoA.Peroxisome-derived lipids promote cellular fitness during hypoxic stress, regulate mitochondrial dynamics to support cold-induced thermogenesis, and control innate immune responses to infectious pathogens.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Fiber release during domestic textile washing is a cause of marine microplastic pollution, but better understanding of the magnitude of the issue and role of fabric care products, appliances and ...washing cycles is needed. Soiled consumer wash loads from U.K. households were found to release a mean of 114 #177; 66.8 ppm (mg microfiber per kg fabric) (n = 79) fibers during typical washing conditions and these were mainly composed of natural fibers. Microfiber release decreased with increasing wash load size and hence decreasing water to fabric ratio, with mean microfiber release from wash loads in the mass range 1.0-3.5 kg (n = 57) found to be 132.4 #177; 68.6 ppm, significantly (p = 3.3 x 10.sup.-8) higher than the 66.3 #177; 27.0 ppm of those in the 3.5-6.0 kg range (n = 22). In further tests with similar soiled consumer wash loads, moving to colder and quicker washing cycles (i.e. 15#176;C for 30 mins, as opposed to 40#176;C for 85 mins) significantly reduced microfiber generation by 30% (p = 0.036) and reduced whiteness loss by 42% (p = 0.000) through reduced dye transfer and soil re-deposition, compared to conventional 40#176;C cycles. In multicycle technical testing, detergent pods were selected for investigation and found to have no impact on microfiber release compared to washing in water alone. Fabric softeners were also found to have no direct impact on microfiber release in testing under both European and North American washing conditions. Extended testing of polyester fleece garments up to a 48-wash cycle history under European conditions found that microfiber release significantly reduced to a consistent low level of 28.7 #177; 10.9 ppm from eight through 64 washes. Emerging North American High-Efficiency top-loading washing machines generated significantly lower microfiber release than traditional top-loading machines, likely due to their lower water fill volumes and hence lower water to fabric ratio, with a 69.7% reduction observed for polyester fleece (n = 32, p = 7.9 x 10.sup.-6) and 37.4% reduction for polyester T-shirt (n = 32, p = 0.0032). These results conclude that consumers can directly reduce the levels of microfibers generated per wash during domestic textile washing by using colder and quicker wash cycles, washing complete (but not overfilled) loads, and (in North America) converting to High-Efficiency washing machines. Moving to colder and quicker cycles will also indirectly reduce microfiber release by extending the lifetime of clothing, leading to fewer new garments being purchased and hence lower incidence of the high microfiber release occurring during the first few washes of a new item.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anthocyanins are a group of pigments that have various roles in plants including attracting pollinators and seed dispersers and protecting against various types of stress. In vegetative tissue, these ...anthocyanins are sequestered in the vacuole following biosynthesis in the cytoplasm, though there remain questions as to the events leading to the vacuolar sequestration. In this study, we were able to show that the uptake of acylated anthocyanins by vacuolar membrane‐enriched vesicles isolated from Arabidopsis was stimulated by the addition of MgATP and was inhibited by both vanadate and glybenclamide, but not by gramicidin D or bafilomycin A1, suggesting that uptake involves an ATP‐binding cassette (ABC) transporter and not an H+‐antiporter. Membrane vesicles isolated from yeast expressing the ABC transporters designated AtABCC1, AtABCC2, and AtABCC14 are capable of MgATP‐dependent uptake of acylated anthocyanins. This uptake was not dependent on glutathione as seen previously for anthocyanidin 3‐O‐monoglucosides. Compared to the wild‐type, the transport of acylated anthocyanins was lower in vacuolar membrane‐enriched vesicles isolated from atabcc1 cell cultures providing evidence that AtABCC1 may be the predominant transporter of these compounds in vivo. In addition, the pattern of anthocyanin accumulation differed between the atabcc1, atabcc2, and atabcc14 mutants and the wild‐type seedlings under anthocyanin inductive conditions. We suggest that AtABCC1, AtABCC2, and AtABCC14 are involved in the vacuolar transport of acylated anthocyanins produced in the vegetative tissue of Arabidopsis and that the pattern of anthocyanin accumulation can be altered depending on the presence or absence of a specific vacuolar ABC transporter.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Autophagy is activated by prolonged fasting but cannot overcome the ensuing hepatic lipid overload, resulting in fatty liver. Here, we describe a peroxisome-lysosome metabolic link that restricts ...autophagic degradation of lipids. Acyl-CoA oxidase 1 (Acox1), the enzyme that catalyzes the first step in peroxisomal β-oxidation, is enriched in liver and further increases with fasting or high-fat diet (HFD). Liver-specific Acox1 knockout (Acox1-LKO) protected mice against hepatic steatosis caused by starvation or HFD due to induction of autophagic degradation of lipid droplets. Hepatic Acox1 deficiency markedly lowered total cytosolic acetyl-CoA levels, which led to decreased Raptor acetylation and reduced lysosomal localization of mTOR, resulting in impaired activation of mTORC1, a central regulator of autophagy. Dichloroacetic acid treatment elevated acetyl-CoA levels, restored mTORC1 activation, inhibited autophagy, and increased hepatic triglycerides in Acox1-LKO mice. These results identify peroxisome-derived acetyl-CoA as a key metabolic regulator of autophagy that controls hepatic lipid homeostasis.
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•Fasting or high-fat diet increases the liver gene expression of Acox1•Acox1-LKO mice are protected against fatty liver through induction of lipophagy•Acetyl-CoA from Acox1-mediated β-oxidation activates mTORC1 and inhibits lipophagy•Pharmacologically increasing acetyl-CoA rescues the phenotype in Acox1-LKO mice
Autophagy is activated by starvation but is not sufficient to prevent the resulting fatty liver. He et al. describe a peroxisome-lysosome crosstalk that restricts autophagic degradation of lipid droplets in the fasted state. They show that acetyl-CoA derived from peroxisomal β-oxidation inhibits lipophagy by promoting Raptor acetylation and mTORC1 activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study sought to better characterize the quality of life and economic impact in patients with symptoms of ischemia and no obstructive coronary disease (INOCA) and to identify the influence of ...coronary microvascular dysfunction (CMD).
Patients with INOCA have a high symptom burden and an increased incidence of major adverse cardiac events. CMD is a frequent cause of INOCA. The morbidity associated with INOCA and CMD has not been well-characterized.
Sixty-six patients with INOCA underwent stress cardiac magnetic resonance with calculation of myocardial perfusion reserve (MPR); MPR 2.0 to 2.4 was considered borderline-reduced (possible CMD) and MPR <2.0 was defined as reduced (definite CMD). Subjects completed quality of life questionnaires to assess the morbidity and economic impact of INOCA. Questionnaire results were compared between INOCA patients with and without CMD. In addition, logistic regression was used to determine the predictors of CMD within the INOCA population.
The prevalence of definite CMD was 24%. Definite or borderline CMD was present in 59% (MPR ≤2.4). Patients with INOCA reported greater physical limitation, angina frequency, and reduced quality of life compared to referent stable coronary artery disease and acute myocardial infarction populations. In addition, Patients with INOCA reported frequent time missed from work and work limitations, suggesting a substantial economic impact. No difference was observed in reported symptoms between INOCA patients with and without CMD. Glomerular filtration rate and body-mass index were significant predictors of CMD in multivariable regression analysis.
INOCA is associated with high morbidity similar to other high-risk cardiac populations, and work limitations reported by Patients with INOCA suggest a substantial economic impact. CMD is a common cause of INOCA but is not associated with increased morbidity. These results suggest that there is significant symptom burden in the INOCA population regardless of etiology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
An approach for assessing the inhalation bioaccessibility of Pb in the PM10 size fraction is presented, using an in vitro simulated epithelial lung fluid to represent the extracellular environment of ...the lung. The developed inhalation bioaccessibility method (IBM) is applied to a range of urban surface soils and mining wastes obtained from Mitrovica, Kosovo, a site where impacts upon human health following exposure to Pb have been internationally publicised. All Pb determinations were undertaken by inductively coupled plasma mass spectrometry (ICP-MS). The pseudo-total concentration of Pb (microwave acid digestion using aqua-regia) varied between matrices: smelter (20,900–72,800mgkg−1), topsoil (274–13,700mgkg−1), and tailings (2990mgkg−1–25,300mgkg−1). The in vitro inhalation bioaccessibility was typically several orders of magnitude lower: smelter (7.0–965mgkg−1), topsoil (9.8–1060mgkg−1), and tailings (0.7mgkg−1–49.2mgkg−1). The % inhalation bioaccessibility ranged from 0.02 to 11.0%, with the higher inhalation bioaccessible Pb concentrations being observed for samples from the Bosniak Mahalla area of Mitrovica (an area proposed for the relocation of internally displaced peoples). The estimated inhalation dose (for adults) calculated from the PM10 pseudo-total Pb concentration ranged from 0.369 to 1.284μgkg−1BWday−1 (smelter), 0.005–0.242μgkg−1BWday−1 (topsoil), and 0.053–0.446μgkg−1BWday−1 (tailings). When daily inhalation doses were calculated using the bioaccessible Pb concentration the modelled exposure doses were much lower: smelter (0.0001–0.0170μgkg−1BWday−1), topsoil (0.0002–0.0187μgkg−1BWday−1) and tailings (0.0001–0.0009μgkg−1BWday−1). Modelled for the neutral pH conditions of the interstitial lung environment, the results indicate a low potential inhalation bioaccessibility for Pb in these samples. Given the already elevated environmental Pb burden experienced by the local population, where significant prolonged dust or particulate generating activities are taking place, or where the inhaled particles are phagocytized, then inhalation exposure has the potential to significantly add to the overall Pb burden. Such data are important for local policy makers to better enable them to assess risk, especially in areas where soils/dusts have elevated levels of contamination.
•Development of a robust approach for assessing the in vitro inhalation bioaccessibility of Pb.•Development of a simulated lung fluid that contains high molecular mass proteins, antioxidants and a surfactant.•Inhalation bioaccessibility of topsoils and mine wastes, from Mitrovica, Kosovo, ranged from 0.02 and 11.0%.•Modelled for the neutral pH of the interstitial lung environment, the samples indicate low Pb inhalation bioaccessibility.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
► Risk of ingestion of PTEs from urban street dust has been assessed. ► Data is compared with other urban street dust samples. ► Comparable data is found except for Pb in a specific sample. ► PTE ...concentrations have been compared to TDI values. ► Oral bioaccessibility of PTEs has been assessed.
The pseudo-total and oral bioaccessible concentration of six potentially toxic elements (PTEs) in urban street dust was investigated. Typical pseudo-total concentrations across the sampling sites ranged from 4.4 to 8.6
mg
kg
−1 for As, 0.2–3.6
mg
kg
−1 for Cd, 25–217
mg
kg
−1 for Cu, 14–46
mg
kg
−1 for Ni, 70–4261
mg
kg
−1 for Pb, and, 111–652
mg
kg
−1 for Zn. This data compared favourably with other urban street dust samples collected and analysed in a variety of cities globally; the exception was the high level of Pb determined in a specific sample in this study. The oral bioaccessibility of PTEs in street dust is also assessed using
in vitro gastrointestinal extraction (Unified Bioaccessibility Method, UBM). Based on a worst case scenario the oral bioaccessibility data estimated that Cd and Zn had the highest % bioaccessible fractions (median >45%) while the other PTEs i.e. As, Cu, Ni and Pb had lower % bioaccessible fractions (median <35%). The pseudo-total and bioaccessible concentrations of PTEs in the samples has been compared to estimated tolerable daily intake values based on unintentional soil/dust consumption. Cadmium, Cu and Ni are well within the oral tolerable daily intake rates. With respect to As and Pb, only the latter exceeds the TDI
oral if we model ingestion rate based on atmospheric ‘dustiness’ rather than the
US EPA (2008) unintentional soil/dust consumption rate of 100
mg
d
−1. We consider it unlikely that even a child with pica tendencies would ingest as much as 100
mg soil/dust during a daily visit to the city centre, and in particular to the sites with elevated Pb concentrations observed in this study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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