LLOMe has long been used to study lysosomal damage, yet how it works has remained a mystery.
Using cryo-electron tomography, we show it forms amyloid structures inside lysosomes that mechanically rupture membranes – revealing a new paradigm for lysosomal failure.
🔗 doi.org/10.64898/202...
#CryoET
Using cryo-electron tomography, we show it forms amyloid structures inside lysosomes that mechanically rupture membranes – revealing a new paradigm for lysosomal failure.
🔗 doi.org/10.64898/202...
#CryoET
January 20, 2026 at 10:01 AM
LLOMe has long been used to study lysosomal damage, yet how it works has remained a mystery.
Using cryo-electron tomography, we show it forms amyloid structures inside lysosomes that mechanically rupture membranes – revealing a new paradigm for lysosomal failure.
🔗 doi.org/10.64898/202...
#CryoET
Using cryo-electron tomography, we show it forms amyloid structures inside lysosomes that mechanically rupture membranes – revealing a new paradigm for lysosomal failure.
🔗 doi.org/10.64898/202...
#CryoET
SO excited to share that a major part of the postdoctoral work in @robzonculab.bsky.social lab is now published: “Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins” www.science.org/doi/10.1126/...
Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins
Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic dataset...
www.science.org
March 27, 2025 at 7:45 PM
SO excited to share that a major part of the postdoctoral work in @robzonculab.bsky.social lab is now published: “Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins” www.science.org/doi/10.1126/...
Out now in @science.org
Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders | Science www.science.org/doi/10.1126/...
Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders | Science www.science.org/doi/10.1126/...
Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders
Lysosomal dysfunction is a well-recognized feature of aging. Here, we used a suite of tools for rapid lysosomal isolation to construct a multitissue atlas of the metabolite changes lysosomes undergo d...
www.science.org
July 31, 2026 at 9:22 AM
Out now in @science.org
Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders | Science www.science.org/doi/10.1126/...
Atlas of lysosomal aging reveals a metabolite signature shared with lysosomal storage disorders | Science www.science.org/doi/10.1126/...
Thrilled to share one of our biggest discoveries: “Inceptor binds to and directs insulin towards lysosomal degradation in beta cells”.
doi.org/10.1038/s422...
A tremendous collaborative effort led by JohannaSiehler, Sara Bilekova and other members of the Lickert lab @heikolickert.bsky.social
doi.org/10.1038/s422...
A tremendous collaborative effort led by JohannaSiehler, Sara Bilekova and other members of the Lickert lab @heikolickert.bsky.social
Inceptor binds to and directs insulin towards lysosomal degradation in β cells - Nature Metabolism
The insulin inhibitory receptor (inceptor) is found to bind to insulin and to regulate insulin stores by directing proinsulin and insulin towards lysosomal degradation.
doi.org
November 25, 2024 at 11:16 AM
Thrilled to share one of our biggest discoveries: “Inceptor binds to and directs insulin towards lysosomal degradation in beta cells”.
doi.org/10.1038/s422...
A tremendous collaborative effort led by JohannaSiehler, Sara Bilekova and other members of the Lickert lab @heikolickert.bsky.social
doi.org/10.1038/s422...
A tremendous collaborative effort led by JohannaSiehler, Sara Bilekova and other members of the Lickert lab @heikolickert.bsky.social
We have developed an entirely new mechanism of action for gene knockdown -> trafficking of targeted mRNAs to the lysosomal, using lysosomal trafficking oligonucleotides (LyTONs)!
Published in @chemicalscience.rsc.org
Led by Disha Kashyap
#chemsky 🧪
pubs.rsc.org/en/content/a...
Published in @chemicalscience.rsc.org
Led by Disha Kashyap
#chemsky 🧪
pubs.rsc.org/en/content/a...
Engineering antisense oligonucleotides for targeted mRNA degradation through lysosomal trafficking
Antisense oligonucleotides (ASOs) can modulate gene expression at the mRNA level, providing the ability to tackle conventionally undruggable targets and usher in an era of personalized medicine. A key...
pubs.rsc.org
June 23, 2025 at 8:01 AM
We have developed an entirely new mechanism of action for gene knockdown -> trafficking of targeted mRNAs to the lysosomal, using lysosomal trafficking oligonucleotides (LyTONs)!
Published in @chemicalscience.rsc.org
Led by Disha Kashyap
#chemsky 🧪
pubs.rsc.org/en/content/a...
Published in @chemicalscience.rsc.org
Led by Disha Kashyap
#chemsky 🧪
pubs.rsc.org/en/content/a...
Excited to share our latest paper in Science Advances! We finally dissected a new pathway for mitochondrial quality control upon mtDNA replication stress! Let’s start a short thread! 🧵
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Retromer promotes the lysosomal turnover of mtDNA
Lysosomal uptake of mtDNA controls mitochondrial quality.
www.science.org
April 4, 2025 at 6:42 PM
Excited to share our latest paper in Science Advances! We finally dissected a new pathway for mitochondrial quality control upon mtDNA replication stress! Let’s start a short thread! 🧵
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
A TBK1/ULK1 signalling axis couples lysosomal stress to TFEB activation
www.nature.com/articles/s41...
www.nature.com/articles/s41...
A TBK1/ULK1 signalling axis couples lysosomal stress to TFEB activation - Nature
Proteomic and phosphoproteomic analyses of lysosomes identify a nutrient-independent regulatory arm of mTORC1 signalling that mediates lysosomal adaptation to stress and whose deregulation underl...
www.nature.com
September 30, 2026 at 6:01 PM
A TBK1/ULK1 signalling axis couples lysosomal stress to TFEB activation
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Nature research paper: A TBK1/ULK1 signalling axis couples lysosomal stress to TFEB activation
go.nature.com/4hvQV05
go.nature.com/4hvQV05
A TBK1/ULK1 signalling axis couples lysosomal stress to TFEB activation - Nature
Proteomic and phosphoproteomic analyses of lysosomes identify a nutrient-independent regulatory arm of mTORC1 signalling that mediates lysosomal adaptation to stress and whose deregulation underlies tumorigenesis in follicular lymphoma.
go.nature.com
October 2, 2026 at 7:15 AM
Nature research paper: A TBK1/ULK1 signalling axis couples lysosomal stress to TFEB activation
go.nature.com/4hvQV05
go.nature.com/4hvQV05
📯 Our paper “VPS13C/PARK23 initiates lipid transfer and membrane remodeling for efficient lysosomal repair” out now in Nature Communications
rdcu.be/frKmN
rdcu.be/frKmN
VPS13C/PARK23 initiates lipid transfer and membrane remodeling for efficient lysosomal repair
Nature Communications - Not all components of the lysosome damage response pathway have been defined. Here, the authors discover that the bridge-like lipid transport protein VPS13C senses lysosomal...
rdcu.be
July 2, 2026 at 8:30 PM
📯 Our paper “VPS13C/PARK23 initiates lipid transfer and membrane remodeling for efficient lysosomal repair” out now in Nature Communications
rdcu.be/frKmN
rdcu.be/frKmN
LYVAC/PDZD8 is a lysosomal vacuolator | Science www.science.org/doi/10.1126/...
LYVAC/PDZD8 is a lysosomal vacuolator
Lysosomal vacuolation is commonly found in many pathophysiological conditions, but its molecular mechanisms and functions remain largely unknown. Here, we show that the endoplasmic reticulum (ER)–anch...
www.science.org
August 21, 2025 at 11:19 PM
LYVAC/PDZD8 is a lysosomal vacuolator | Science www.science.org/doi/10.1126/...
mTORC1 activity licenses its own release from the lysosomal surface
www.cell.com/molecular-ce...
www.cell.com/molecular-ce...
mTORC1 activity licenses its own release from the lysosomal surface
The activation of mTORC1 is intricately linked to its subcellular localization, with
the Rag GTPases controlling its lysosomal recruitment in response to nutrient cues.
Acharya and Demetriades uncover...
www.cell.com
November 23, 2024 at 11:13 AM
mTORC1 activity licenses its own release from the lysosomal surface
www.cell.com/molecular-ce...
www.cell.com/molecular-ce...
#WeekendRead! #NotOnlyInterferons! @nanyanlab.bsky.social &co show @cp-molecularcell.bsky.social that other than inducing pathogenic IFNs in lysosomal storage disorders, STING also play protective functions as a proton channel activating TFEB & inducing lysosomal repair www.cell.com/molecular-ce...
STING mediates lysosomal quality control and recovery through its proton channel function and TFEB activation in lysosomal storage disorders
STING signaling in the innate immune system is well known for its role in the antiviral
type I interferon response. Tang et al. find that STING acts as an immune sensor of
lysosomal activity. When the...
www.cell.com
April 5, 2025 at 3:08 PM
#WeekendRead! #NotOnlyInterferons! @nanyanlab.bsky.social &co show @cp-molecularcell.bsky.social that other than inducing pathogenic IFNs in lysosomal storage disorders, STING also play protective functions as a proton channel activating TFEB & inducing lysosomal repair www.cell.com/molecular-ce...
Proud to share a preprint of our paper on how bridge-like lipid transport protein VPS13C senses lysosomal membrane tension in anticipation of membrane lesions to initiate net ER-to-lysosome lipid transfer for efficient lysosomal repair www.biorxiv.org/content/10.1...
VPS13C/PARK23 initiates lipid transfer and membrane remodeling for efficient lysosomal repair
Perturbations in lysosome integrity are tightly linked to neurological disorders and ageing, but the underlying pathogenic mechanisms are incompletely understood. Using an unbiased proteomic approach,...
www.biorxiv.org
October 25, 2025 at 1:11 PM
Proud to share a preprint of our paper on how bridge-like lipid transport protein VPS13C senses lysosomal membrane tension in anticipation of membrane lesions to initiate net ER-to-lysosome lipid transfer for efficient lysosomal repair www.biorxiv.org/content/10.1...
A new #ScienceImmunology study shows that deleting the lysosomal protein Flcn from regulatory T cells can prevent their accumulation in some tissues, thus boosting antitumor immunity in mice. https://scim.ag/4o1g1of
Mitochondrial and lysosomal signaling orchestrates heterogeneous metabolic states of regulatory T cells
Mitochondrial and lysosomal signaling orchestrates Treg cell metabolic states and functional fitness.
scim.ag
October 28, 2025 at 3:40 PM
A new #ScienceImmunology study shows that deleting the lysosomal protein Flcn from regulatory T cells can prevent their accumulation in some tissues, thus boosting antitumor immunity in mice. https://scim.ag/4o1g1of
Are u tired of reading about tariffs? Then take a look to our last work! @science.org
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Retromer promotes the lysosomal turnover of mtDNA
Lysosomal uptake of mtDNA controls mitochondrial quality.
www.science.org
April 4, 2025 at 6:07 PM
Are u tired of reading about tariffs? Then take a look to our last work! @science.org
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
my first #FluorescenceFriday post! Mouse hippocampus showing microglia, a lysosomal marker (CD68), and Aggrecan, a perineuronal net component. 😍 Image by Dr. Julia Dziabis!
November 7, 2025 at 6:55 PM
my first #FluorescenceFriday post! Mouse hippocampus showing microglia, a lysosomal marker (CD68), and Aggrecan, a perineuronal net component. 😍 Image by Dr. Julia Dziabis!
Lysosomal storage diseases are like a hundred different targets lol
March 29, 2026 at 4:05 PM
Lysosomal storage diseases are like a hundred different targets lol
New work from Coon Lab (Wisconsin), @harperlabhms.bsky.social & Gygi Lab @harvardcellbio.bsky.social reports global proteomics/lipidomics of > 2 dozen Lysosomal Storage Disease mutant cells & reveals iron defects associated with mitochondrial defects in NPC2 mutants www.science.org/doi/10.1126/...
Global cellular proteo-lipidomic profiling of diverse lysosomal storage disease mutants using nMOST
A nanoflow multiomic workflow reveals how lysosomal dysfunction disrupts autophagy and mitochondrial homeostasis in LSD mutants.
www.science.org
January 22, 2025 at 7:43 PM
New work from Coon Lab (Wisconsin), @harperlabhms.bsky.social & Gygi Lab @harvardcellbio.bsky.social reports global proteomics/lipidomics of > 2 dozen Lysosomal Storage Disease mutant cells & reveals iron defects associated with mitochondrial defects in NPC2 mutants www.science.org/doi/10.1126/...
Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins | Science www.science.org/doi/10.1126/...
Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins
Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic dataset...
www.science.org
March 27, 2025 at 10:40 PM
Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins | Science www.science.org/doi/10.1126/...
H. Meyer is starting the afternoon session with lysosomal damage and ubiquitin signalling #EMBOUbiquitin
September 29, 2026 at 1:32 PM
H. Meyer is starting the afternoon session with lysosomal damage and ubiquitin signalling #EMBOUbiquitin
Great to see our work on the #cryoem structure of the human TSC:WIPI3 lysosomal recruitment complex! Awesome effort from co-authors @charlesbj.bsky.social and Laura D'Andrea with @drellisdon.bsky.social doing the heavy lifting leading the project.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
Structure of the human TSC:WIPI3 lysosomal recruitment complex
The complete TSC structure reveals how lysosomal targeting proteins and phosphoinositides coordinate mTORC1 inhibition.
www.science.org
November 21, 2024 at 12:35 AM
Great to see our work on the #cryoem structure of the human TSC:WIPI3 lysosomal recruitment complex! Awesome effort from co-authors @charlesbj.bsky.social and Laura D'Andrea with @drellisdon.bsky.social doing the heavy lifting leading the project.
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes!
Annexin A11 tethers RNP granules to membranes in a Ca2+ dependent manner.
@abelljonny.bsky.social, @michael-e-ward.bsky.social, et al.
www.nature.com/articles/s41...
Annexin A11 tethers RNP granules to membranes in a Ca2+ dependent manner.
@abelljonny.bsky.social, @michael-e-ward.bsky.social, et al.
www.nature.com/articles/s41...
ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes - Nature Communications
Nixon-Abell et al. show that ANXA11 condensation on lysosomal membranes causes a coupled phase transition of the underlying lipids and mechanical stiffening of the overall ensemble involved in RNP gra...
www.nature.com
March 23, 2025 at 9:25 AM
ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes!
Annexin A11 tethers RNP granules to membranes in a Ca2+ dependent manner.
@abelljonny.bsky.social, @michael-e-ward.bsky.social, et al.
www.nature.com/articles/s41...
Annexin A11 tethers RNP granules to membranes in a Ca2+ dependent manner.
@abelljonny.bsky.social, @michael-e-ward.bsky.social, et al.
www.nature.com/articles/s41...
Thrilled to share our latest work @luptoncj.bsky.social @drellisdon.bsky.social @drmlhalls.bsky.social.
Structure of the lysosomal KICSTOR-GATOR1-SAMTOR nutrient-sensing supercomplex.
🧪🔬#cryoEM
Now online @cellpress.bsky.social.
doi.org/10.1016/j.ce...
Structure of the lysosomal KICSTOR-GATOR1-SAMTOR nutrient-sensing supercomplex.
🧪🔬#cryoEM
Now online @cellpress.bsky.social.
doi.org/10.1016/j.ce...
January 8, 2026 at 7:39 PM
Thrilled to share our latest work @luptoncj.bsky.social @drellisdon.bsky.social @drmlhalls.bsky.social.
Structure of the lysosomal KICSTOR-GATOR1-SAMTOR nutrient-sensing supercomplex.
🧪🔬#cryoEM
Now online @cellpress.bsky.social.
doi.org/10.1016/j.ce...
Structure of the lysosomal KICSTOR-GATOR1-SAMTOR nutrient-sensing supercomplex.
🧪🔬#cryoEM
Now online @cellpress.bsky.social.
doi.org/10.1016/j.ce...
An incredible tour de force in biochemistry and cell biology by superstar @robzonculab.bsky.social lab postdoc @aakritijain.bsky.social
LyLAP - a new lysosomal protease responsible for degrading integral membrane proteins in highly phagocytic cells like #PDAC cells.
www.science.org/doi/10.1126/...
LyLAP - a new lysosomal protease responsible for degrading integral membrane proteins in highly phagocytic cells like #PDAC cells.
www.science.org/doi/10.1126/...
Leucine aminopeptidase LyLAP enables lysosomal degradation of membrane proteins
Breakdown of every transmembrane protein trafficked to lysosomes requires proteolysis of their hydrophobic helical transmembrane domains. Combining lysosomal proteomics with functional genomic dataset...
www.science.org
March 28, 2025 at 7:13 PM
An incredible tour de force in biochemistry and cell biology by superstar @robzonculab.bsky.social lab postdoc @aakritijain.bsky.social
LyLAP - a new lysosomal protease responsible for degrading integral membrane proteins in highly phagocytic cells like #PDAC cells.
www.science.org/doi/10.1126/...
LyLAP - a new lysosomal protease responsible for degrading integral membrane proteins in highly phagocytic cells like #PDAC cells.
www.science.org/doi/10.1126/...
Review @cp-cellchembiol.bsky.social @volkerhaucke-lab.bsky.social
Mechanisms and functions of lysosomal lipid homeostasis
www.cell.com/cell-chemica...
Mechanisms and functions of lysosomal lipid homeostasis
www.cell.com/cell-chemica...
Mechanisms and functions of lysosomal lipid homeostasis
In this review Ebner et al. summarize and discuss the rapidly increasing knowledge
regarding the mechanisms of lysosomal lipid turnover and export as well as the pathways
for the homeostatic control a...
www.cell.com
March 7, 2025 at 6:20 PM
Review @cp-cellchembiol.bsky.social @volkerhaucke-lab.bsky.social
Mechanisms and functions of lysosomal lipid homeostasis
www.cell.com/cell-chemica...
Mechanisms and functions of lysosomal lipid homeostasis
www.cell.com/cell-chemica...