Deacetylated SNAP47 recruits HOPS to facilitate autophagosome-lysosome fusion independent of STX17.

Autophagy, a conserved catabolic process implicated in a diverse array of human diseases, requires efficient fusion between autophagosomes and lysosomes to function effectively. Recently, SNAP47 has been identified as a key component of the dual-purpose SNARE complex mediating autophagosome-lysosome fusion in both bulk and selective autophagy. However, the spatiotemporal regulatory mechanisms of this SNARE complex remain unknown.

The STX17-SNAP47-VAMP7/VAMP8 complex is the default SNARE complex mediating autophagosome-lysosome fusion.

Autophagosome-lysosome fusion mediated by SNARE complexes is an essential step in autophagy. Two SNAP29-containing SNARE complexes have been extensively studied in starvation-induced bulk autophagy, while the relevant SNARE complexes in other types of autophagy occurring under non-starvation conditions have been overlooked. Here, we found that autophagosome-lysosome fusion in selective autophagy under non-starvation conditions does not require SNAP29-containing SNARE complexes, but requires the STX17-SNAP47-VAMP7/VAMP8 SNARE complex.

ULK phosphorylation of STX17 controls autophagosome maturation via FLNA.

Autophagy is a conserved and tightly regulated intracellular quality control pathway. ULK is a key kinase in autophagy initiation, but whether ULK kinase activity also participates in the late stages of autophagy remains unknown. Here, we found that the autophagosomal SNARE protein, STX17, is phosphorylated by ULK at residue S289, beyond which it localizes specifically to autophagosomes.

Bifendate inhibits autophagy at multiple steps and attenuates oleic acid-induced lipid accumulation.

Some traditional Chinese medicines exert roles in the therapy of liver diseases by modulating autophagy. Bifendate (DDB), a synthetic intermediate of Schisandrin C extracted from Schisandrae chinensis, is clinically used to treat hepatitis in China. While DDB is a positive control to research some potential hepatoprotective agents, its related molecular mechanisms are unknown.

Recycling of autophagosomal components from autolysosomes by the recycler complex.

Autolysosomes contain components from autophagosomes and lysosomes. The contents inside the autolysosomal lumen are degraded during autophagy, while the fate of autophagosomal components on the autolysosomal membrane remains unknown. Here we report that the autophagosomal membrane components are not degraded, but recycled from autolysosomes through a process coined in this study as autophagosomal components recycling (ACR).

Sam50 Regulates PINK1-Parkin-Mediated Mitophagy by Controlling PINK1 Stability and Mitochondrial Morphology.

PINK1 and Parkin mediate mitophagy, the cellular process that clears dysfunctional mitochondria. Mitophagy is regulated by mitochondrial dynamics, but the molecules linking these two processes remain poorly understood. Here, we show that Sam50, the core component of the sorting and assembly machinery (SAM), is a critical regulator of mitochondrial dynamics and PINK1-Parkin-mediated mitophagy.

The roles of DNA damage-dependent signals and MAPK cascades in tributyltin-induced germline apoptosis in Caenorhabditis elegans.

The induction of apoptosis is recognized to be a major mechanism of tributyltin (TBT) toxicity. However, the underlying signaling pathways for TBT-induced apoptosis remain unclear. In this study, using the nematode Caenorhabditis elegans, we examined whether DNA damage response (DDR) pathway and mitogen-activated protein kinase (MAPK) signaling cascades are involved in TBT-induced germline apoptosis and cell cycle arrest.

Stress-response protein expression and DAF-16 translocation were induced in tributyltin-exposed Caenorhabditis elegans.

Exposure to tributyltin (TBT) with graded sublethal doses (0, 1, 10, 50 and 200 nM) resulted in the release of reactive oxygen species (ROS) and DNA damage in the nematode Caenorhabditis elegans. After the worms carrying transgenic reporters were exposed to TBT, the expressions of superoxide dismutase (SOD-3), glutathione S-transferase (GST-4) and heat shock proteins (HSP-4, HSP-16.2 and HSP-70) were semi-quantified after exposure.