PtdIns(3)P plays critical roles in the autophagy pathway. However, little is known about how PtdIns(3)P effectors act with autophagy proteins in autophagosome formation. Here we identified an essential autophagy gene in C. elegans, epg-6, which encodes a WD40 repeat-containing protein with PtdIns(3)P-binding activity. EPG-6 directly interacts with ATG-2. epg-6 and atg-2 regulate progression of omegasomes to autophagosomes, and their loss of function causes accumulation of enlarged early autophagic structures. Another WD40 repeat PtdIns(3)P effector, ATG-18, plays a distinct role in autophagosome formation. We also established the hierarchical relationship of autophagy genes in degradation of protein aggregates and revealed that the UNC-51/Atg1 complex, EPG-8/Atg14, and binding of lipidated LGG-1 to protein aggregates are required for omegasome formation. Our study demonstrates that autophagic PtdIns(3)P effectors play distinct roles in autophagosome formation and also provides a framework for understanding the concerted action of autophagy genes in protein aggregate degradation.
The mechanism by which nutrient status regulates the fusion of autophagosomes with endosomes/lysosomes is poorly understood. Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. O-GlcNAcylated SNAP-29 levels are reduced during starvation in mammalian cells and in C. elegans. Our study reveals a mechanism by which O-GlcNAc-modification integrates nutrient status with autophagosome maturation.
Covalent organic frameworks (COFs) with reversible redox behaviors are potential electrode materials for lithium‐ion batteries (LIBs). However, the sluggish lithium diffusion kinetics, poor electronic conductivity, low reversible capacities, and poor rate performance for most reported COF materials limit their further application. Herein, a new 2D COF (TFPB‐COF) with six unsaturated benzene rings per repeating unit and ordered mesoporous pores (≈2.1 nm) is designed. A chemical stripping strategy is developed to obtain exfoliated few‐layered COF nanosheets (E‐TFPB‐COF), whose restacking is prevented by the in situ formed MnO2 nanoparticles. Compared with the bulk TFPB‐COF, the exfoliated TFPB‐COF exhibits new active Li‐storage sites associated with conjugated aromatic π electrons by facilitating faster ion/electron kinetics. The E‐TFPB‐COF/MnO2 and E‐TFPB‐COF electrodes exhibit large reversible capacities of 1359 and 968 mAh g−1 after 300 cycles with good high‐rate capability.
units, SBUs) and coordinated organic ligands via the more flexible coordination bonds, which results in the controllable morphology and pore characteristic. [1f,g] Induced by these structural merits, COF and MOF have been widely applied in gas storage/separation, catalysis, and photoelectric conversion, and even the field of energy storage including Li-ion batteries, supercapacitors, and hydrogen storage. [2] In order to effectively combine the merits of COF and MOF and acquire the maximized performances, there are few recent reports regarding the hybridization of COF and MOF. [3] By introducing the as-prepared MOF into the synthetic process of COF, MOF@COF core-shell [3a,b] or MOF-coated COF [3c] hybrids were obtained. All these hybrids have been demonstrated with excellent photocatalytic performances as the effective photocatalysts/photocatalysis platforms for degradation of rhodamine B, [3a] dehydrogenation of ammonia borane, [3b] and H 2 evolution, [3c] respectively. This kind of approach (introducing the as-prepared MOF into the synthetic process of COF) would result in the comparatively simple combination of COF and MOF with core-shell or coating composite mode (no principal morphology change), and the molecular-level interlinked hybridization between COF and MOF remains unexplored.For the purpose of property optimization, intimate hybridization between two components is highly desirable, which may lead to further morphology adjustment, and consequent performance improvement. Considering the fact that organic groups from COF may also coordinate with metal ions of MOF, we design a COF/Mn-MOF hybrid structure with flower-like morphology, which is different from pristine COF or Mn-MOF. A strong synergistic effect relative to new active sites from MOF and COF for lithium storage is observed in the composite. Hollow or coreshell microspheres of MnS@N/S codoped carbon can also be derived with superior electrochemical properties.The COF/Mn-MOF composite with benchmarked pristine COF or Mn-MOF ( Figure S1a,b, Supporting Information) was characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR), Raman and 13 C nuclear magnetism measurements in Figure S2a-d (Supporting Information). All characteristic diffraction peaks for Mn-MOF [4] can be detected for COF/ Mn-MOF with clear shift to small angle for its two main peaks (2θ ≈ 10.5° and ≈21.7°), which is probably originated from the Covalent organic frameworks (COF) or metal-organic frameworks have attracted significant attention for various applications due to their intriguing tunable micro/mesopores and composition/functionality control. Herein, a coordination-induced interlinked hybrid of imine-based covalent organic frameworks and Mn-based metal-organic frameworks (COF/Mn-MOF) based on the MnN bond is reported. The effective molecular-level coordinationinduced compositing of COF and MOF endows the hybrid with unique flower-like microsphere morphology and superior lithium-storage performances that originate from activated Mn centers an...
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