RESUMO
Although once perceived as inert structures that merely serve for lipid storage, lipid droplets (LDs) have proven to be the dynamic organelles that hold many cellular functions. The LDs' basic structure of a hydrophobic core consisting of neutral lipids and enclosed in a phospholipid monolayer allows for quick lipid accessibility for intracellular energy and membrane production. Whereas formed at the peripheral and perinuclear endoplasmic reticulum, LDs are degraded either in the cytosol by lipolysis or in the vacuoles/lysosomes by autophagy. Autophagy is a regulated breakdown of dysfunctional, damaged, or surplus cellular components. The selective autophagy of LDs is called lipophagy. Here, we review LDs and their degradation by lipophagy in yeast, which proceeds via the micrometer-scale raft-like lipid domains in the vacuolar membrane. These vacuolar microdomains form during nutrient deprivation and facilitate internalization of LDs via the vacuolar membrane invagination and scission. The resultant intra-vacuolar autophagic bodies with LDs inside are broken down by vacuolar lipases and proteases. This type of lipophagy is called microlipophagy as it resembles microautophagy, the type of autophagy when substrates are sequestered right at the surface of a lytic compartment. Yeast microlipophagy via the raft-like vacuolar microdomains is a great model system to study the role of lipid domains in microautophagic pathways.
Assuntos
Autofagia/fisiologia , Gotículas Lipídicas/metabolismo , Microdomínios da Membrana/metabolismo , Saccharomyces cerevisiae/metabolismo , Vacúolos/metabolismo , Citosol/metabolismo , Retículo Endoplasmático/metabolismo , Homeostase/fisiologia , Lipólise/fisiologia , Lisossomos/metabolismo , Fosfolipídeos/metabolismoRESUMO
COVID-19 has profoundly impacted global livelihoods and disrupted the food supply chain, including the aquaculture and fisheries industries. Little is known about the response to COVID-19 and the impact it has on incomes, livelihoods and knowledge and practice in the coastal artisanal fishers communities of Bangladesh. Therefore, the aim of this study was to determine the socio-demographics of selected coastal fishers, their knowledge about COVID-19 and the preventive practice taken to reduce it. The impact on their fishing habits and income was also examined to determine potential policy areas. Data were collected via a structured questionnaire from 250 respondents from three coastal districts, Cox's Bazar, Patuakhali and Barguna, Bangladesh during April-June 2020. The research shows that the fishers' knowledge about COVID-19 and measures taken to reduce it were significantly higher in Patuakhali and Barguna than in Cox's Bazar. The pandemic caused lower consumer demand, reduced fish prices and created fish transportation issues due to movement restrictions enforced during the lockdown. Irrespective of geographical location, fishing trips were reduced by frequency and duration compared with the pre-COVID-19 period, consequently lowering the income of fishers. Fishers have received little or no support from private, non-governmental or governmental sources. Considering the evidence in this paper of economic hardship, this paper recommends artisanal fishers in Bangladesh should be provided with support to improve their health education, access to professional health facilities and financial services. This will contribute to improved food security and sustainable livelihoods that can better withstand local and/or global crises.
RESUMO
In yeast, the selective autophagy of intracellular lipid droplets (LDs) or lipophagy can be induced by either nitrogen (N) starvation or carbon limitation (e.g., in the stationary (S) phase). We developed the yeast, Komagataella phaffii (formerly Pichia pastoris), as a new lipophagy model and compared the N-starvation and S-phase lipophagy in over 30 autophagy-related mutants using the Erg6-GFP processing assay. Surprisingly, two lipophagy pathways had hardly overlapping stringent molecular requirements. While the N-starvation lipophagy strictly depended on the core autophagic machinery (Atg1-Atg9, Atg18, and Vps15), vacuole fusion machinery (Vam7 and Ypt7), and vacuolar proteolysis (proteinases A and B), only Atg6 and proteinases A and B were essential for the S-phase lipophagy. The rest of the proteins were only partially required in the S-phase. Moreover, we isolated the prl1 (for the positive regulator of lipophagy 1) mutant affected in the S-phase lipophagy, but not N-starvation lipophagy. The prl1 defect was at a stage of delivery of the LDs from the cytoplasm to the vacuole, further supporting the mechanistically different nature of the two lipophagy pathways. Taken together, our results suggest that N-starvation and S-phase lipophagy have distinct molecular mechanisms.
Assuntos
Autofagia , Nitrogênio/deficiência , Saccharomycetales/metabolismo , Proteínas Fúngicas/metabolismo , Modelos Biológicos , Mutação/genética , Fenótipo , Fase S , Saccharomycetales/citologia , Vacúolos/metabolismoRESUMO
Nucleolar proteins such as Nop1/fibrillarin are degraded by nucleophagy in nutrient-starved conditions. However, whether and how excess nucleolar proteins are removed in normal conditions is unknown. Here we show that overexpressed nucleolar protein Nop1 is toxic and degraded in nutrient-rich conditions in budding yeast. The degradation was dependent on proteasomes. The CUE domain-containing protein Def1 mediated the degradation via the CUE domain and alleviated toxicity of Nop1 overexpression. Def1 was recruited to overexpressed Nop1 in the nucleolus. Ubiquitin mutants compromised this recruitment. This study revealed that Def1 is a novel factor for ubiquitin-dependent degradation of excess nucleolar proteins.
Assuntos
Proteínas Cromossômicas não Histona/metabolismo , Proteínas Nucleares/metabolismo , Ribonucleoproteínas Nucleolares Pequenas/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Ubiquitina/genética , Ubiquitina/metabolismoRESUMO
Nutrient starvation and inactivation of target of rapamycin complex 1 (TORC1) protein kinase promotes macroautophagy. Macroautophagy is a lipid-consuming process, and Nem1/Spo7 protein phosphatase and Pah1/lipin phosphatidate phosphatase are activated after TORC1 inactivation, supporting macroautophagy induction in the budding yeast Saccharomyces cerevisiae. On the other hand, whether and how microautophagy, which also consumes lipids, is regulated by TORC1 is controversial. Here we show that TORC1 inactivation induces microautophagy in budding yeast. Vps27, but not Atg1, Atg7, or Atg8, was required for TORC1 inactivation-induced microautophagy. Furthermore, the Nem1/Spo7-Pah1 axis was also critical for microautophagy induction. Thus, the TORC1-Nem1/Spo7-Pah1 axis is a master regulator of not only macroautophagy but also microautophagy in budding yeast.
Assuntos
Autofagia , Proteínas de Membrana/metabolismo , Proteínas Nucleares/metabolismo , Fosfatidato Fosfatase/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Saccharomycetales , Sirolimo/químicaRESUMO
Marine fish are good source of essential macro- and micronutrients and major food items in coastal areas in Bangladesh. However, there is no review that details the nutritional value of marine fish in Bangladesh. Therefore, this review focuses on the nutrient composition of marine fish in Bangladesh and how the marine fish can address common nutrient deficiencies among women and children. Nutrient composition data was collected through literature searching in databases and source, including PubMed, Web of Science, Google Scholar, ScienceDirect, WorldFish, and Bangladesh-based database Banglajol. Calculation was carried out to present how one serving marine fish could potentially meet the daily requirement of protein, iron, zinc, calcium, vitamin A, and docosahexaenoic acid (DHA) for pregnant and lactating women and children aged 6-23 months. A total of 97 entries covering nutrient composition analysis of 67 individual fish species were extracted from 12 articles published between 1993 and 2020. Included articles contained analysis of proximate composition, vitamins, minerals, fatty acids, and amino acid. Twelve minerals and nine vitamins were analyzed and reported. The average energy, protein, fat, and ash content per 100 g edible raw marine fish was 343.58 kJ, 16.76 g, 4.16 g, and 2.22 g, respectively. According to available data, marine fish are good sources of protein, zinc, calcium, and DHA. Pelagic small fish, which are mainly captured by artisanal small-scale fishers, had more nutritional value than other categories of fish. Furthermore, marine small fish were found more nutritious than commonly consumed freshwater fish types in Bangladesh, including major carps, introduced carps, and tilapia. Therefore, the study concludes that marine fish have high potential to address malnutrition in Bangladesh. There was scarcity of literature regarding the nutrient composition of marine fish in Bangladesh and in South Asia as a whole, so more comprehensive quality research in this area is recommended.
RESUMO
Virtual reality exposure therapy (VRET) is a novel intervention technique that allows individuals to experience anxiety-evoking stimuli in a safe environment, recognise specific triggers and gradually increase their exposure to perceived threats. Public-speaking anxiety (PSA) is a prevalent form of social anxiety, characterised by stressful arousal and anxiety generated when presenting to an audience. In self-guided VRET, participants can gradually increase their tolerance to exposure and reduce anxiety-induced arousal and PSA over time. However, creating such a VR environment and determining physiological indices of anxiety-induced arousal or distress is an open challenge. Environment modelling, character creation and animation, psychological state determination and the use of machine learning (ML) models for anxiety or stress detection are equally important, and multi-disciplinary expertise is required. In this work, we have explored a series of ML models with publicly available data sets (using electroencephalogram and heart rate variability) to predict arousal states. If we can detect anxiety-induced arousal, we can trigger calming activities to allow individuals to cope with and overcome distress. Here, we discuss the means of effective selection of ML models and parameters in arousal detection. We propose a pipeline to overcome the model selection problem with different parameter settings in the context of virtual reality exposure therapy. This pipeline can be extended to other domains of interest where arousal detection is crucial. Finally, we have implemented a biofeedback framework for VRET where we successfully provided feedback as a form of heart rate and brain laterality index from our acquired multimodal data for psychological intervention to overcome anxiety.
RESUMO
Unsatisfied kinetochore-microtubule attachment activates the spindle assembly checkpoint to inhibit the metaphase-anaphase transition. However, some cells eventually override mitotic arrest by mitotic slippage. Here, we show that inactivation of TORC1 kinase elicits mitotic slippage in budding yeast and human cells. Yeast mitotic slippage was accompanied with aberrant aspects, such as degradation of the nucleolar protein Net1, release of phosphatase Cdc14, and anaphase-promoting complex/cyclosome (APC/C)-Cdh1-dependent degradation of securin and cyclin B in metaphase. This mitotic slippage caused chromosome instability. In human cells, mammalian TORC1 (mTORC1) inactivation also invoked mitotic slippage, indicating that TORC1 inactivation-induced mitotic slippage is conserved from yeast to mammalian cells. However, the invoked mitotic slippage in human cells was not dependent on APC/C-Cdh1. This study revealed an unexpected involvement of TORC1 in mitosis and provides information on undesirable side effects of the use of TORC1 inhibitors as immunosuppressants and anti-tumor drugs.
RESUMO
The blue swimming crab (Portunus pelagicus Linnaeus, 1758) is one of the commercially exploited crab fishery resources in Vietnam. This is the first study to provide a broad survey of genetic diversity, population structure and migration patterns of P. pelagicus along the Vietnamese coastline. The crab samples were collected from northern, central and southern Vietnam. Here, we used a panel of single nucleotide polymorphisms (SNPs) generated from restriction site-associated DNA sequencing (RADseq). After removing 32 outlier loci, 306 putatively neutral SNPs from 96 individuals were used to assess fine-scale population structure of blue swimming crab. The mean observed heterozygosity (Ho) and expected heterozygosity (He) per locus was 0.196 and 0.223, respectively. Pairwise Fst and hierarchical AMOVA supported significant differentiation of central and northern from southern populations (P<0.01). Population structure analyses revealed that P. pelagicus in the south is a separate fisheries unit from the north and center. Contemporary migration patterns supported high migration between northern and central populations and restricted genetic exchange within the southern population. In contrast, historic gene flow provides strong evidence for single panmictic population. The results are useful for understanding current status of P. pelagicus in the wild under an environment changing due to natural and anthropogenic stresses, with implications for fisheries management.
Assuntos
Braquiúros/genética , Pesqueiros/estatística & dados numéricos , Fluxo Gênico , Animais , Feminino , Masculino , Polimorfismo de Nucleotídeo Único , Dinâmica Populacional/estatística & dados numéricos , Análise de Sequência de DNA , VietnãRESUMO
Nutrient starvation and inactivation of target of rapamycin complex 1 (TORC1) protein kinase induce nucleophagy preferentially degrading only nucleolar components in budding yeast. Nucleolar proteins are relocated to sites proximal to the nucleus-vacuole junction (NVJ), where micronucleophagy occurs, whereas rDNA, which is embedded in the nucleolus under normal conditions, moves to NVJ-distal regions, causing rDNA dissociation from nucleolar proteins after TORC1 inactivation. This repositioning is mediated via chromosome linkage INM protein (CLIP)-cohibin complexes that tether rDNA to the inner nuclear membrane. Here, we show that TORC1 inactivation-induced rDNA condensation promotes the repositioning of rDNA and nucleolar proteins. Defects in condensin, Rpd3-Sin3 histone deacetylase (HDAC), and high-mobility group protein 1 (Hmo1), which are involved in TORC1 inactivation-induced rDNA condensation, compromised the repositioning and nucleophagic degradation of nucleolar proteins, although rDNA still escaped from nucleophagic degradation in these mutants. We propose a model in which rDNA condensation after TORC1 inactivation generates a motive force for the repositioning of rDNA and nucleolar proteins.
Assuntos
Autofagia/imunologia , DNA Ribossômico/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas Nucleares/metabolismo , HumanosRESUMO
Autophagy is a process that requires intense membrane remodeling and consumption. The nutrient-responsive TORC1 (target of rapamycin complex 1) kinase regulates autophagy. However, how TORC1 controls autophagy via lipid/membrane biogenesis is unknown. TORC1 regulates the function of yeast phosphatidate phosphatase lipin Pah1 via the Nem1/Spo7 phosphatase complex. Here, we show that the Nem1/Spo7-Pah1 axis is required for autophagy induction after TORC1 inactivation and survival during starvation. Furthermore, this axis was critical for nucleophagy (both micronucleophagy and macronucleophagy) and was required for proper localization of micronucleophagy factor Nvj1 and macronucleophagy receptor Atg39. This study indicated that the Nem1/Spo7-Pah1 axis controlled by TORC1 is a critical branch for autophagy induction in nutrient starvation conditions.
Assuntos
Autofagia/fisiologia , Proteínas de Saccharomyces cerevisiae/fisiologia , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/antagonistas & inibidores , Núcleo Celular/metabolismo , Mitocôndrias/metabolismo , Nitrogênio/metabolismo , Fosfatidato Fosfatase/metabolismo , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
Nutrient starvation or inactivation of target of rapamycin complex 1 (TORC1) in budding yeast induces nucleophagy, a selective autophagy process that preferentially degrades nucleolar components. DNA, including ribosomal DNA (rDNA), is not degraded by nucleophagy, even though rDNA is embedded in the nucleolus. Here, we show that TORC1 inactivation promotes relocalization of nucleolar proteins and rDNA to different sites. Nucleolar proteins move to sites proximal to the nuclear-vacuolar junction (NVJ), where micronucleophagy (or piecemeal microautophagy of the nucleus) occurs, whereas rDNA dissociates from nucleolar proteins and moves to sites distal to NVJs. CLIP and cohibin, which tether rDNA to the inner nuclear membrane, were required for repositioning of nucleolar proteins and rDNA, as well as effective nucleophagic degradation of the nucleolar proteins. Furthermore, micronucleophagy itself was necessary for the repositioning of rDNA and nucleolar proteins. However, rDNA escaped from nucleophagic degradation in CLIP- or cohibin-deficient cells. This study reveals that rDNA-nucleolar protein separation is important for the nucleophagic degradation of nucleolar proteins.