Vesicle Nucleation Research Articles

Shock‐induced pervasive remelting of Fe sulfides in the basaltic shergottite Northwest Africa 14672: A benchmark for shock stages S6/S7 on Mars

AbstractNorthwest Africa (NWA) 14672, the most highly shocked Martian meteorite so far, has experienced >50% melting, compatible with peak pressure >~65 Gpa, at a transition stage 6/7. Despite these extreme shock conditions, the meteorite still preserves a population of “large” Fe sulfide blebs from the pre‐shock igneous assemblage. These primary blebs preserve characteristics of basaltic shergottites in term of modal abundance, preferential occurrence in interstitial pores along with late‐crystallized phases (ilmenite, merrillite), and Ni‐free pyrrhotite compositions. Primary sulfides underwent widespread shock‐induced remelting, as indicated by perfect spherical morphologies when embedded in fine‐grained silicate melt zones and a wealth of mineral/glass/vesicle inclusions. Extensive melting of Fe‐sulfides is consistent with the decompression path experienced by NWA 14672 after the peak shock pressure at ~70 GPa. Primary sulfides acted as preferential sites for nucleation of vesicles of all sizes which helped sulfur degassing during decompression, leading to partial resorption of Fe‐sulfide blebs and reequilibration of pyrrhotite metal/sulfur ratios (0.96–0.98) toward the low oxygen fugacity conditions indicated by Fe‐Ti oxides hosted in fine‐grained materials. The extreme shock intensity also provided suitable conditions for widespread in situ redistribution of igneous sulfur as micrometric globules concentrated in glassy portions of fine‐grained lithologies. These globules exsolved early on quenching, allowing dendritic skeletal Fe‐Ti oxide overgrowths to nucleate on sulfides.

Textural Study of Vesicles in Tagish Lake (C2-ung) Meteorite Fusion Crust: Constraints on Vesicle Formation during Their Entry into the Earth’s Atmosphere

Vesicles are characteristic structures within the outer layer of many stony meteorites’ fusion crusts. Although these features are well-developed in hydrated carbonaceous chondrites and some micrometeorites, their formation mechanism remains poorly understood. This study provides new insights into the understanding of physical vesiculation processes by presenting the results of vesicle size distribution (VSD)—i.e., a quantitative method for vesicle analysis—applied to the study of the Tagish Lake (C2-ung) meteorite fusion crust. Tagish Lake was chosen because it shows a scoriaceous texture and a significant number of vesicles (about 24,000 vesicles/mm2), thus allowing statistical analysis. Vesicles range from being spherical to irregular-shaped and from a few μm to ~70 μm (equivalent diameter) in size. Vesicle size distribution and cumulative number density analyses show a high nucleation event and a fractal distribution of the vesicle population, respectively. We suggest these features are due to disequilibrium degassing processes, which simultaneously produce continuous/accelerating vesicle nucleation and growth. Finally, possible analogies between the scoriaceous Tagish Lake fusion crust and the space-weathered “frothy layer” on the surface of Ryugu’s grains could be found in terms of vesicularity.

The role of lysosomal membrane proteins in autophagy and related diseases.

As a self-degrading and highly conserved survival mechanism, autophagy plays an important role in maintaining cell survival and recycling. The discovery of autophagy-related (ATG) genes has revolutionized our understanding of autophagy. Lysosomal membrane proteins (LMPs) are important executors of lysosomal function, and increasing evidence has demonstrated their role in the induction and regulation of autophagy. In addition, the functional dysregulation of the process mediated by LMPs at all stages of autophagy is closely related to neurodegenerative diseases and cancer. Here, we review the role of LMPs in autophagy, focusing on their roles in vesicle nucleation, vesicle elongation and completion, the fusion of autophagosomes and lysosomes, and degradation, as well as their broad association with related diseases.

Mechanosensitive (de)regulation of exosome production in tumors.

Cells release membrane-bound nanovesicles (extracellular vesicles) as efficient modes for cell-to-cell communication. Exosomes are nanovesicles produced through the endocytic pathway (involving inwards budding of the endosomal membrane to form multivesicular endosomes, MVEs) and secreted via exocytosis. Tumor-derived exosomes (TEXs) have been implicated in cancer progression and metastasis, with studies showing their role in promoting tumor cell invasion, immune evasion, and pre-metastatic niches. Tumors also leverage dysregulated extracellular matrix (ECM) remodeling mechanisms to create a conducive microenvironment. One such essential mechanical alteration is the stiffening of ECM, which enhances oncogenic signaling pathways leading to tumor progression. Recent experiments have demonstrated ECM stiffness-dependent exosome secretion in various cancer cell lines with higher exosome release on stiff matrix. To capture this mechanobiology-based regulatory axis hijacked by tumors, we suggest a two-pronged mechanosensitive modulation of TEXs. First, using a mesoscale membrane model evolved with Monte Carlo techniques based on the Helfrich Hamiltonian, we show that stiff ECM modulates exosome formation through its effect on cortical tension. Our results suggest an ultrasensitive response of vesicle nucleation induced by curvature-inducing proteins to changes in cortical tension. Second, experimental collaborators have observed Akt-dependent activation of Rabin8 (Guanine Exchange Factor (GEF) of Rab8) along with increased Rab8-mediated exosome secretion on a stiff matrix for transformed cell lines. We capture this mechanosensitive signaling pathway, involved in directing MVE transport to the cellular membrane for exosome release, using an ODE model. Exosome secretion can then be quantified as the combination of formation and trafficking of MVEs. These coarse-grain predictions agree with the experimentally observed change in exosome amount as the matrix stiffens.

Gallstones: The thing in itself.

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Stage-specific and location-specific cartilage calcification in osteoarthritis development

ObjectivesThis study investigated the stage-specific and location-specific deposition and characteristics of minerals in human osteoarthritis (OA) cartilages via multiple nano-analytical technologies.MethodsNormal and OA cartilages were serially sectioned for micro-CT, scanning...

Role of Collagen in Vascular Calcification.

Vascular calcification is a pathological process characterized by ectopic calcification of the vascular wall. Medial calcifications are most often associated with kidney disease, diabetes, hypertension, and advanced age. Intimal calcifications are associated with atherosclerosis. Collagen can regulate mineralization by binding to apatite minerals and promoting their deposition, binding to collagen receptors to initiate signal transduction, and inducing cell transdifferentiation. In the process of vascular calcification, type I collagen is not only the scaffold for mineral deposition but also a signal entity, guiding the distribution, aggregation, and nucleation of vesicles and promoting the transformation of vascular smooth muscle cells into osteochondral-like cells. In recent years, collagen has been shown to affect vascular calcification through collagen disc-domain receptors, matrix vesicles, and transdifferentiation of vascular smooth muscle cells.

Bubbles and atom clusters in rock melts: A chicken and egg problem

Bubble and crystal nucleation and growth dynamics play a vital function in determining the eruptive behaviour of a magma. Investigating the initial stages of bubble nucleation and crystallization processes, including their rate and relative timing, can thus give us insight into the eruption parameters of magmas including their rheology. Although many experiments and numerical simulations of decompression-induced vesicle nucleation in magmas have been carried out, the mechanisms of bubble nucleation remain poorly understood. It is widely accepted that there are two ways bubbles can form: either by homogeneous nucleation within a melt, or by heterogeneous nucleation on a surface, interface, or particle. It has been tentatively suggested that what had been interpreted as homogeneous nucleation in magmas was instead heterogeneous nucleation on the surface of elusive nano- or micro-scale crystals present throughout the melt. Herein, we have conducted an experiment whereby bubble nucleation is induced in a synthetic andesitic glass sample using radiation damage from a focused ion beam (FIB) to investigate the initial stages of bubble nucleation. Scanning transmission electron microscopy, electron energy-loss spectroscopy and atom probe tomography (APT) data reveal sub-nanometer scale chemical heterogeneities in the form of Fe-, Na-, and/or Ca-rich clusters at the bubble-glass interface of the newly created bubbles. Comparatively, specimens prepared by cryogenic FIB, in which bubble nucleation is suppressed, are without bubbles; however, APT data shows similar chemical heterogeneities suggesting these clusters existed within the synthetic glass prior to bubble formation. Based on these observations, our data demonstrate the existence of nanoscale chemical heterogeneities within a synthetic silicate glass and at bubble-glass interfaces. Although our experiments do not replicate the conditions of natural processes, our results contribute to the hypothesis that previously described homogeneous nucleation may be re-interpreted as a variety of heterogeneous nucleation. These findings highlight the need to revise the commonly used definition of homogeneous nucleation among magma scientists.

The involvement of PyBeclin 1 and PyLC3 in regulating the activation of autophagy in scallop Patinopecten yessoensis after acute high temperature stress

Beclin 1 and LC3 are important autophagy regulation proteins involved in vesicle nucleation and extension stage, respectively. In the present study, a Beclin 1 and a LC3 were identified from Yesso scallop Patinopecten yessoensis (PyBeclin 1 and PyLC3). The open reading frame (ORF) of PyBeclin 1 was of 1335 bp encoding a putative polypeptide of 444 amino acid residues with an N-terminal BCL-2 homology 3 (BH3) domain, a central coiled-coil domain (CCD), and a C-terminal evolutionarily conserved domain (ECD). The ORF of PyLC3 was of 369 bp encoding a putative polypeptide of 122 amino acid residues with an APG12 domain. The deduced amino acid sequences of PyBeclin 1 and PyLC3 shared 31.92–74.09% and 68.38–79.50% identities with Beclin 1s and LC3s from other species, respectively. The mRNA transcripts of PyBeclin 1 and PyLC3 were found to be expressed in all the examined tissues, including adductor muscle, gonad, gill, haemocytes and mantle, with the highest expression level in gill and haemocytes. The mRNA expression level of PyBeclin 1 in haemocytes increased significantly at 1, 3, 6, 12 and 24 h (2.98–4.07 fold of that in the Blank group, p < 0.05), and returned to normal level at 48 h after acute high temperature stress at 25 °C. Unlike PyBeclin 1, the mRNA transcripts of PyLC3 in haemocytes were significantly up-regulated at1, 3, 6 and 12 h (1.80–2.54 fold of that in the Blank group, p < 0.05), then decreased to blank level at 24 h (p > 0.05), and increased significantly again at 48 h (3.70 fold of that in the Blank group, p < 0.05) after high temperature. PyBeclin 1 and PyLC3 were mainly located in the cytoplasm and a small amount in the nucleus with few puncta, and the numbers of PyBeclin 1 and PyLC3 puncta increased at 3 h after acute high temperature stress. The LC3-II levels in gill and haemocytes were significantly up-regulated at 1 h and 3 h after acute high temperature stress. These results collectively suggested that PyBeclin 1 and PyLC3 were conserved members of Beclin 1 and LC3 family in scallops, and involved in regulating the activation of autophagy in scallops after acute high temperature stress.

Evolution of magma decompression and discharge during a Plinian event (Late Bronze-Age eruption, Santorini) from multiple eruption-intensity proxies

We have coupled three independent methods to investigate the time evolution of eruptive intensity during the sub-Plinian and Plinian phases of the 3600-year BP Late Bronze-Age eruption of Santorini Volcano: (1) mass eruption rate based on new lithic isopleth maps for multiple layers of the fall deposit, (2) magma decompression rate calculated from vesicle number densities, and (3) magma decompression rate calculated from H2O gradients in melt reentrants, with methods 2 and 3 measured on the same suite of pyroclasts. Mass eruption rate increased by two orders of magnitude, reaching 210 × 106 kg s−1 at the peak of the Plinian phase (plume height 28.4 ± 1.0 km); it then declined in the final stage of fallout emplacement following the first generation of pyroclastic surges. Decompression rates from melt reentrants (0.008 to 0.25 MPa s−1) are two to three orders of magnitude lower than those from vesicle number densities, assuming heterogeneous vesicle nucleation (2 to 19 MPa s−1). Melt reentrants are thought to record slow decompression in the deep feeder conduit, whereas vesicles record much higher rates of decompression in the shallow conduit due to the steep, nonlinear pressure gradients associated with magma vesiculation and fragmentation. Upwardly converging flow from a dike-like, deep conduit to a more cylindrical, shallow conduit may also have played a role in causing upwardly accelerating flow. Variations in deep decompression rate recorded by melt reentrants are decoupled from mass eruption rate, whereas those recorded by vesicles lie in between. Taken with the transition from unsteady to steady Plinian eruption, this may reflect the existence of transient flow conditions in the conduit system due to widening and lengthening of a deep feeder dike as Plinian eruption progressed. As the mass eruption rate rose to its peak value, the fragmentation level fell in the conduit due to increasing rates of magma strain and decompression.

Optimality in Self-Organized Molecular Sorting.

We introduce a simple physical picture to explain the process of molecular sorting, whereby specific proteins are concentrated and distilled into submicrometric lipid vesicles in eukaryotic cells. To this purpose, we formulate a model based on the coupling of spontaneous molecular aggregation with vesicle nucleation. Its implications are studied by means of a phenomenological theory describing the diffusion of molecules toward multiple sorting centers that grow due to molecule absorption and are extracted when they reach a sufficiently large size. The predictions of the theory are compared with numerical simulations of a lattice-gas realization of the model and with experimental observations. The efficiency of the distillation process is found to be optimal for intermediate aggregation rates, where the density of sorted molecules is minimal and the process obeys simple scaling laws. Quantitative measures of endocytic sorting performed in primary endothelial cells are compatible with the hypothesis that these optimal conditions are realized in living cells.

Decrypting silicic magma/plug fragmentation at Azufral crater lake, Northern Andes: insights from fine to extremely fine ash morpho-chemistry

Azufral (SW Colombia) is a dangerous silicic volcano hosting a crater lake, which serves as an excellent example of an incipient plug disruption through phreatomagmatism. We studied the youngest succession of dilute pyroclastic density currents (PDCs) onlapping the north-eastern crater rim. Scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy was used to carry out an automated single-particle analysis of fine to extremely fine ash. We were able to obtain fast and accurate chemical analysis and imaging of 15,098 particles within the 250–63-μm and the 63–32-μm size ranges. The 2D form and roughness parameters were determined for 4895 juvenile glassy particles and validated by 3D micro-X ray computer tomography. There are two end members of high (group 1) and low (group 2) roughness juvenile glassy particles. Group 1 comprises high-roughness glass particles with solidity values as low as 0.34 in 2D and 0.33 in 3D, and convexity values as low as 0.33 in 2D and 0.26 in 3D. Group 2 comprises low-roughness glass particles with 2D solidity values > 0.79 and 3D solidity values typically > 0.58. In this group, 2D convexity values are > 0.68 and 3D convexity values are > 0.71. Both end members are mostly discriminated by the 2D Concavity Index (0.14 to 0.77 in group 1 vs. 0.05–0.35 in group 2). The remaining group 3 comprises particles of intermediate roughness values. In this study, we show how an incipient plug developed over a short repose time might be subjected to only a few cycles of vesicle nucleation, collapse and densification, retaining the characteristics of juvenile glass. Each glassy juvenile ash type, defined by a particular morphology, roughness and microtexture can be linked to a density “stratified” conduit model. In Azufral, the capping and conduit lining dense regions and the permeable zones of the incipient plug likely cracked. The newly formed cracks could allow hydraulic forcing caused by external water and induce phreatomagmatic interaction. This interaction favoured the fine fragmentation of the plug while enhancing ongoing magmatic processes. Finally, the variations of bulk componentry provided clues on dilute pyroclastic density current transport and physical fractionation processes by secondary fragmentation, elutriation and interaction with the crater rim.

Harnessing Autophagic Network Is Essential for Trophoblast Stem Cell Differentiation.

Differentiation of trophoblast stem (TS) cells into various cell lineages of the placenta during mammalian development is accompanied by dynamic changes in its proteome for exerting the highly specialized functions of various cell subtypes. In the present study, we demonstrate that the autophagic machinery, which includes proteins for initiation, vesicle nucleation, and autophagosome maturation are robustly upregulated during differentiation of TS cells. Interestingly, basal levels of autophagy were detectable in the developing mouse placenta as well as TS cells. However, autophagic flux was actively triggered by induction of differentiation evident from LC3 maturation. Formation of Beclin1, Vps34, and PIK3R4 ternary complex at the phagophore assembly site that is typically known to induce autophagy was also enhanced during differentiation. Degradation of the p62/SQSTM1 cargo protein and its colocalization with LC3, a mature autophagosome marker, was most prevalent in the trophoblast giant cells (TGCs) and negligible in other trophoblast cells at day 6 of differentiation. Furthermore, disruption of autophagy by impairing lysosomal fusion in TS cells before induction of differentiation led to a decrease in the giant cell and spongiotrophoblast cell markers Prl3d1, Prl2c2, Prl4a1, and Tpbpα upon differentiation. In addition, inhibition of autophagy was associated with a decrease in nuclear size of TGCs. Taken together, these data highlight that autophagy is a necessary prelude in commitment of trophoblast differentiation from the multipotent TS cells probably by regulating protein turnover at the onset of differentiation.

Autophagic Proteome in Two Saccharomyces cerevisiae Strains During Second Fermentation for Sparkling Wine Elaboration.

A correlation between autophagy and autolysis has been proposed in order to accelerate the acquisition of wine organoleptic properties during sparkling wine elaboration. In this context, a proteomic analysis was carried out in two industrial Saccharomyces cerevisiae strains (P29, conventional sparkling wine strain and G1, implicated in sherry wine elaboration) with the aim of studying the autophagy-related proteome and comparing the effect of CO2 overpressure during sparkling wine elaboration. In general, a detrimental effect of pressure and second fermentation development on autophagy-related proteome was observed in both strains, although it was more pronounced in flor yeast strain G1. Proteins mainly involved in autophagy regulation and autophagosome formation in flor yeast G1, and those required for vesicle nucleation and expansion in P29 strain, highlighted in sealed bottle. Proteins Sec2 and Sec18 were detected 3-fold under pressure conditions in P29 and G1 strains, respectively. Moreover, ‘fingerprinting’ obtained from multivariate data analysis established differences in autophagy-related proteome between strains and conditions. Further research is needed to achieve more solid conclusions and design strategies to promote autophagy for an accelerated autolysis, thus reducing cost and time production, as well as acquisition of good organoleptic properties.

Molecular mechanisms of non-coding RNA regulating autophagy and interventional effects of Chinese herbal medicine

Long non-coding RNAs(lncRNAs) and microRNAs(miRNAs),as members of the non-coding RNA family,play important roles in upstream processes that regulate autophagy in mammalian cells. LncRNA and miRNA participate in various phases of the process of autophagy,including initiation,vesicle nucleation,autophagosome maturation and autophagosome fusion. Some non-coding RNAs exert bidirectional regulatory functions in the process of autophagy,include the maternally expressed gene 3(MEG3),H19 and miR-21,whereas others either inhibit autophagy(including GAS5,miR-34 a and miR-30 a) or promote autophagy(including MALAT1,miR-152 and miR-24). The regulation of autophagy by non-coding RNAs has characteristics of conditionality,diversity and complexity. In recent years,researchers at home and abroad have constantly found that some extracts from the individual Chinese herbal medicine(CHM) such as ampelopsin,salvianolic acid B and paeonol,as well as the Chinese herbal compound named Eight Ingredients Decoction,can regulate autophagy by interacting with non-coding RNA in vitro and in vivo. The latest studies have shown that plant-derived small non-coding RNAs(sncRNAs) as one of the active ingredients of CHMs can directly enter the bloodstream and internal organs to regulate gene expressions in humans. In addition,it has been reported that rhein,hyperoside and mycelium of Cordyceps sinensis all can modulate autophagy in renal tubular epithelial cell via regulating the autophagy-related signaling pathways in vivo and in vitro to reduce renal damage and aging,which is likely mediated by the miR-34 a pathway. In summary,the understanding of molecular mechanisms underlying the regulation of autophagy by non-coding RNAs(such as lncRNAs and miRNAs) is essential and required to develop new strategies for the treatments and managements of tumors,immune diseases,metabolic diseases,neurodegenerative diseases and other common diseases and decipher pharmacologic actions of CHMs.

Driving mechanisms of subaerial and subglacial explosive episodes during the 10th century Eldgjá fissure eruption, southern Iceland

The 10th century Eldgjá fissure eruption is the largest in Iceland in historical time. It erupted 21.0 km3 of magma, with 1.3 km3 as tephra in at least 16 explosive episodes from subaerial and subglacial vents, producing magmatic and phreatomagmatic deposits respectively. Grain-size distributions for these end-members show distinct differences at comparable distances from source: the former are coarser and unimodal; the latter are finer and bimodal. These distributions appear to record different primary fragmentation histories. In contrast, the vesicle-size distributions of pyroclasts from each type of deposit show the pyroclasts underwent similar vesicle nucleation and growth prior to fragmentation. This indicates that the role of glacial water was comparatively late-stage, re-fragmenting an already disrupting magma by quench granulation. The presence of microlite-rich domains within clasts reveals a history of complex conduit evolution, during the transition from a continuous dyke to focussed, discrete vents.

Molecular Lipid Films on Microengineering Materials.

In this study, we have systematically investigated the formation of molecular phospholipid films on a variety of solid substrates fabricated from typical surface engineering materials and the fluidic properties of the lipid membranes formed on these substrates. The surface materials comprise of borosilicate glass, mica, SiO2, Al (native oxide), Al2O3, TiO2, ITO, SiC, Au, Teflon AF, SU-8, and graphene. We deposited the lipid films from small unilamellar vesicles (SUVs) by means of an open-space microfluidic device, observed the formation and development of the films by laser scanning confocal microscopy, and evaluated the mode and degree of coverage, fluidity, and integrity. In addition to previously established mechanisms of lipid membrane-surface interaction upon bulk addition of SUVs on solid supports, we observed nontrivial lipid adhesion phenomena, including reverse rolling of spreading bilayers, spontaneous nucleation and growth of multilamellar vesicles, and the formation of intact circular patches of double lipid bilayer membranes. Our findings allow for accurate prediction of membrane-surface interactions in microfabricated devices and experimental environments where model membranes are used as functional biomimetic coatings.

Differential Expression of Autophagy-Related Marker (Beclin-1) in Relation to Clinicopathological Parameters in Different Breast Cancer Molecular Subtypes

AbstractBackground: Beclin-1 plays a vital role in the vesicle nucleation in the process of autophagy and has an important role in development, tumorigenesis, and neurodegeneration.Aim of Study: Study the role of beclin-1 and correlate the degree of its expression with available clinic-pathological data in different molecular types of breast cancer.Material and Methods: Immunohistochemistry was per-formed to examine the expression of Beclin-1 different mo-lecular subtypes of invasive ductal carcinoma and correlating it to clinicopathological parameter.Results: The expression of Beclin-1 was decreased in breast cancer in relation to normal tissue. High expression was significantly correlated with tumor grade, distant metas-tasis and stage. All the cases with high Beclin-1 expression were triple negative breast cancer cases.Conclusions: Triple negative breast cancer cases showed the highest tumor stage, grade, distant metastasis and beclin-1 expression suggesting that the overexpression of Beclin 1 may by itself confer an aggressive biological course. It could be a therapeutic target.

Autophagy: novel insights into therapeutic target of electroacupuncture against cerebral ischemia/ reperfusion injury.

Electroacupuncture is known as an effective adjuvant therapy in ischemic cerebrovascular disease. However, its underlying mechanisms remain unclear. Studies suggest that autophagy, which is essential for cell survival and cell death, is involved in cerebral ischemia reperfusion injury and might be modulate by electroacupuncture therapy in key ways. This paper aims to provide novel insights into a therapeutic target of electroacupuncture against cerebral ischemia/reperfusion injury from the perspective of autophagy. Here we review recent studies on electroacupuncture regulation of autophagy-related markers such as UNC-51-like kinase-1 complex, Beclin1, microtubule-associated protein-1 light chain 3, p62, and autophagosomes for treating cerebral ischemia/reperfusion injury. The results of these studies show that electroacupuncture may affect the initiation of autophagy, vesicle nucleation, expansion and maturation of autophagosomes, as well as fusion and degradation of autophagolysosomes. Moreover, studies indicate that electroacupuncture probably modulates autophagy by activating the mammalian target of the rapamycin signaling pathway. This review thus indicates that autophagy is a therapeutic target of electroacupuncture treatment against ischemic cerebrovascular diseases.

Abstract 1349: Functional and mechanistic characterization of PRMT6 regulated autophagy in hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) is a major health burden worldwide. Tumor recurrence and therapy resistance represent major obstacles in the treatment of the disease, with their mechanism of action largely uncharacterized. Autophagy is a critical survival factor for cancer cells, whereby it maintains cellular homeostasis including degradation of damaged organelles and unwanted proteins as well as the support of cellular biosynthesis in response to environmental stress, preventing cells from undergoing apoptosis. Our group has recently reported on the regulatory role of protein arginine methyltransferase 6 (PRMT6) down-regulation in maintenance of HCC, particularly potentiating resistance to sorafenib and chemotherapy. By tandem affinity purification/mass spectrometry analysis of cells with PRMT6 stably overexpressed, we identified a number of autophagy related proteins as potential interacting partners of PRMT6, suggesting a possible role of PRMT6 in modulating autophagy in HCC. Treatment of HCC cells with stress induced conditions, including sorafenib, nutrient deprivation and hypoxic condition, resulted in a marked reduction of PRMT6 expression, concomitant with elevated levels of LC3BII. Further, under these various stimuli, knockdown of PRMT6 in HCC cells would also result in enhanced expression of LC3BII, accumulation of GFP-LC3B positive puncta staining as well as an increase in autophagosome formation. Consistently, treatment of HCC cells with PRMT6 overexpressed would leading to an opposing effect. Further studies by immunoprecipitation analysis validated PRMT6 to physically interact with AMBRA1 (activating molecule in BECN1-regulated autophagy protein 1), a well-known autophagy initiative component, which takes part in autophagy vesicle nucleation, a critical step for autophagic initiation. Our findings suggest PRMT6 down-regulation in HCC tumors to promote tumorigenicity through autophagic flux de-regulation. Targeting the mechanisms of stress response may provide novel therapeutic insights for the disease. Citation Format: Noélia Che, Man Tong, Kai Yu Ng, Phillis WF Kau, Xin Yuan Guan, Michael SY Huen, Stephanie Ma. Functional and mechanistic characterization of PRMT6 regulated autophagy in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1349.