Autophagy in Disease and Therapy

Autophagy protects pancreatic β-cells during hypoxia and islet transplantation but is compromised by TFEB-lysosomal dysfunction

The human leukemic fusion protein MLL-AF4 promotes autophagy and cell death in the fat body of Drosophila melanogaster

The paper shows that the human MLL-AF4 fusion protein induces autophagy and cell death in Drosophila fat body cells, contrasting its effect in the hematopoietic system.

Vertical inhibition of the autophagy pathway impairs growth and enhances sensitivity to mTORC1 inhibition in pancreatic ductal adenocarcinoma

This study identifies that vertical inhibition of the autophagy pathway enhances sensitivity to mTORC1 inhibition in PDAC, improving therapeutic efficacy.

Basal BNIP3/NIX mitophagy is controlled by selective protection of sentinel receptors

The paper identifies ARMC1 as a repressor of mitophagy that interacts with TMEM11, BNIP3, and NIX, and shows TMEM11 antagonizes PPTC7 to protect receptors during mitophagy activation.

ROS Impair Mitophagy via PARylation of PINK1

This study shows that ROS inhibit mitophagy by activating PARP1, which PARylates PINK1 and impairs its function.

Autophagy suppresses microglial activation and enhances M2 polarization via the mTOR/ULK1 pathway after optic nerve crush

This study shows rapamycin enhances autophagy and M2 microglial polarization by inhibiting the mTOR/ULK1 pathway in vivo and in vitro.

Atg23 Interacts With Both the N- and C-termini of Atg9 Via a Hydrophobic Binding Pocket

This study determines the crystal structure of Atg23 and identifies hydrophobic interactions between Atg23 and both N- and C-terminal regions of Atg9.

Autophagy is suppressed in peripheral blood mononuclear cells during chronic obstructive pulmonary disease.

The paper shows that autophagy is suppressed in peripheral blood mononuclear cells of COPD patients, as indicated by reduced autophagic flux and fewer autophagy-related vacuoles.

Alpha-2-Macroglobulin/LRP1 signaling promotes mitochondrial clearance and autophagic extracellular vesicle release in erythroid cells

This study shows that 2M* activates mitophagy and promotes EV release via LRP1 in erythroid cells, linking autophagy and vesicular trafficking.

Glucose concentration of neuronal media formulations influences PINK1-dependent mitophagy in human iNeurons

This study shows that glucose levels in neuronal culture media affect PINK1-dependent mitophagy in human iNeurons, with BrainPhys medium reducing mitophagy compared to N2B27.

The ESCRT-0 protein HRS regulates hepatocellular lipid droplet catabolism

This paper identifies HRS as a regulator of lipid droplet catabolism in hepatocytes, showing it affects LD-lysosomal targeting and lysosomal function.

Lipid transfer protein ORP3 mediates lysosomal repair via LC3B and ubiquitin-TAK1-p38

This paper identifies ORP3 as a lipid transfer protein that mediates lysosomal repair through interactions with LC3B and the TAK1-p38 signaling pathway.

Canonical autophagy remains inactive in induced pluripotent stem cells and neuronal progenitor cells following DNA damage induced by BPDE or etoposide.

This study shows that canonical autophagy remains inactive in iPSCs and NPCs under DNA damage, despite a functional autophagy machinery and responsive DNA damage response.

Characterization of a novel neurodevelopmental rare disease caused by a mutation within the autophagy gene ATG9B

The paper reports a novel neurodevelopmental disorder caused by a frameshift mutation in ATG9B, and characterizes its effects using cell models and knock-in mice.

ATG16L2 creates a VAIL-dedicated heterodimer with ATG16L1

This study identifies ATG16L2 as a specialized regulator of VAIL-selective ATG8 lipidation, forming a functional heterodimer with ATG16L1.

ATG7 function promotes pancreatic cancer progression independently of autophagy

This study identifies ATG7(2) as a driver of pancreatic cancer progression independent of autophagy, showing its role in promoting proliferation, migration, and tumor growth.

Sephin1 rewires proteostasis through actin-dependent signaling

This study identifies sephin1's mechanism of action in proteostasis disruption by showing it binds G-actin, causes cytoskeleton misfolding, and modulates autophagy through mTORC1-TFEB and GCN2-eIF2-CHOP pathways.

Synphilin-1 mitigates autophagy dysfunction, modulates ubiquitinated protein aggregation, and promotes cell survival during proteotoxic stress

This study shows Synphilin-1 helps cells survive proteotoxic stress by managing ubiquitinated protein aggregation and autophagy dysfunction in WHAMM/JMY knockout fibroblasts.

Declining autophagy drives age-related axonal decay through microtubule alterations

This study shows that declining autophagy in aged neurons leads to microtubule alterations, causing axonal and synaptic decay, and that enhancing autophagy can reverse these effects.

Structural basis for the ATP-dependence of omegasome biogenesis by DFCP1

This paper determines the crystal structures of DFCP1's ATPase domain with ADP and ATP analogues, revealing structural elements that regulate ATP hydrolysis and omegasome dynamics.

A multi-subunit autophagic capture complex facilitates degradation of ER stalled MHC-I in pancreatic cancer.

This study identifies a multi-subunit autophagic capture complex that degrades ER-stalled MHC-I in pancreatic cancer, reducing immunogenicity.

Two-photon in vivo imaging reveals cell type-specific mitophagy dynamic changes in mouse somatosensory cortex during aging

This study uses two-photon imaging to show that mitophagy decreases with age in mouse somatosensory cortex neurons and astrocytes, with astrocytes showing higher mitophagy levels than neurons, and NAD+ treatment improves mitophagy in aged mice.

Pathogenic variants in autophagy-tethering factor EPG5 drive neurodegeneration through mitochondrial dysfunction and innate immune activation

This study identifies EPG5 mutations causing neurodegeneration via mitochondrial dysfunction and innate immune activation in patient-derived cells.

MITF is essential for autophagy in the retinal pigment epithelium

This study shows that MITF regulates autophagy in RPE cells, with reduced MITF causing autophagy defects and lysosomal dysfunction linked to retinal degeneration.

The V-ATPase/ATG16L1 axis drives membrane remodeling during epithelial morphogenesis

The paper shows the V-ATPase/ATG16L1 axis is essential for de novo lumen formation during epithelial tube morphogenesis.

A Rosella-PLIN2 Knock-in Mouse Reveals Lipophagy and Immunometabolic Interplay in Atherosclerosis

This study uses a Rosella-PLIN2 biosensor to track lipophagy in atherosclerosis, revealing cell-specific differences in lipid metabolism and immunometabolic interactions.

Autophagy flux during human aging is sex- and cell type-specific, and is associated with physical fitness

This study examines autophagy flux changes with age in human cell types, finding sex- and cell-type-specific patterns and a link to physical fitness.

High basal autophagic activity in the brain revealed by systemic quantitative analysis using GFP-LC3-RFP mice

This study quantifies basal autophagic flux in mice using GFP-LC3-RFP reporter mice, revealing higher flux in brain, liver, and kidney compared to other tissues.

Pathway-selective mitophagy regulates retinal physiology and neurogenic transitions in Muller glia

This study identifies distinct mitophagy pathways in Muller glia and their role in retinal physiology and neurogenic transitions.

Acute lysosome repositioning reveals functional and proteomic adaptations

The paper develops a method to reposition lysosomes and identifies proteomic differences between perinuclear and peripheral lysosomes.