Wilfling Lab
@wilflinglab.bsky.social
Investigating mechanisms of eukaryotic cellular quality control with a focus on autophagy @MPIbp via #cryoET, #teamtomo, #cellbiology and #massspectrometry
Pinned
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
Also check out a fantastic complementary study from the Jeffery Kelly lab! They independently uncover how LLOMe disrupts lysosomes by forming amyloids that may act as seeds for pathological aggregates
🔗 doi.org/10.64898/202...
🔗 doi.org/10.64898/202...
Cathepsin C–Catalyzed Ligation Generates Intralysosomal Amyloid Fibrils from Dipeptide Esters
Amyloid fibril-associated endolysosomal dysfunction is implicated in multiple neurodegenerative diseases. We report the rapid generation of intralysosomal amyloid fibrils by simply treating cells with certain dipeptide methyl esters. Cathepsin C mediates the ligation of dipeptides into oligopeptides that, sequence-dependently, self-assemble into amyloid fibrils. Progressive fibril growth, not fibril deposition, mediates lysosomal membrane permeabilization. Cryo-electron tomography studies reveal intralysosomal fibrils and broken lysosomal membranes upon dipeptide treatment. Certain oligopeptide fibril structures are competent to cross-seed the aggregation of neurodegeneration-associated Tau(P301S) at lysosomal sites. Similarly, the degree of lysosomal membrane permeabilization and ESCRT-repair response can be tuned with dipeptide sequence variation. The presented Cathepsin C-dependent amyloid fibril formation approach lends itself toward the development of novel tools to further probe lysosomal biology and pathobiology. ### Competing Interest Statement The authors have declared no competing interest. National Institute on Aging, https://ror.org/049v75w11, RF1AG073418 National Center for Advancing Translational Sciences, https://ror.org/04pw6fb54 Department of Education, USA, P031S240270 Freedom Together Foundation Chan Zuckerberg Initiative (United States), CZII-2023–327779 George E. Hewitt Foundation for Medical Research
doi.org
January 20, 2026 at 10:09 AM
Also check out a fantastic complementary study from the Jeffery Kelly lab! They independently uncover how LLOMe disrupts lysosomes by forming amyloids that may act as seeds for pathological aggregates
🔗 doi.org/10.64898/202...
🔗 doi.org/10.64898/202...
Huge thanks to all amazing co-authors and collaborators — this work was a true team effort! @mmedina300kv.bsky.social @nanigrotjahn.bsky.social @andschwarz.bsky.social @erin-schuman.bsky.social @sauerkrausi.bsky.social @harperlabhms.bsky.social @sonjawelsch.bsky.social @hummerlab.bsky.social
January 20, 2026 at 10:07 AM
Huge thanks to all amazing co-authors and collaborators — this work was a true team effort! @mmedina300kv.bsky.social @nanigrotjahn.bsky.social @andschwarz.bsky.social @erin-schuman.bsky.social @sauerkrausi.bsky.social @harperlabhms.bsky.social @sonjawelsch.bsky.social @hummerlab.bsky.social
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
Many thanks to first authors @emboyle.bsky.social, @sergiocruzleon.bsky.social, @structjavi.bsky.social and Johann Brenner and our fantastic collaborators from the Kraft @kraftlabfr.bsky.social, Hummer @hummerlab.bsky.social, Milles @millessigrid.bsky.social and Hunte labs for all their great work!
January 13, 2026 at 2:39 PM
Many thanks to first authors @emboyle.bsky.social, @sergiocruzleon.bsky.social, @structjavi.bsky.social and Johann Brenner and our fantastic collaborators from the Kraft @kraftlabfr.bsky.social, Hummer @hummerlab.bsky.social, Milles @millessigrid.bsky.social and Hunte labs for all their great work!
In this study we investigate the architecture of aminopeptidase-1 condensates directly inside cells at molecular resolution! We show how transient local structures can mediate phase separation, directly linking amino acid sequence to condensate material properties and biological function.
January 13, 2026 at 2:39 PM
In this study we investigate the architecture of aminopeptidase-1 condensates directly inside cells at molecular resolution! We show how transient local structures can mediate phase separation, directly linking amino acid sequence to condensate material properties and biological function.
We are excited to share our new preprint which is now available to read on biorXiv: doi.org/10.64898/202... 🎉🎉🎉
January 13, 2026 at 2:39 PM
We are excited to share our new preprint which is now available to read on biorXiv: doi.org/10.64898/202... 🎉🎉🎉
Many thanks to first authors @emboyle.bsky.social, @sergiocruzleon.bsky.social, @structjavi.bsky.social and Johann Brenner and our fantastic collaborators from the Kraft @kraftlabfr.bsky.social, Hummer @hummerlab.bsky.social, Milles @millessigrid.bsky.social and Hunte labs for all their great work!
January 13, 2026 at 2:34 PM
Many thanks to first authors @emboyle.bsky.social, @sergiocruzleon.bsky.social, @structjavi.bsky.social and Johann Brenner and our fantastic collaborators from the Kraft @kraftlabfr.bsky.social, Hummer @hummerlab.bsky.social, Milles @millessigrid.bsky.social and Hunte labs for all their great work!
Yes was absolute fun! Like always a fantastic collaboration.
Physical principles have redefined our understanding of autophagy.
In our new @cp-trendsbiochem.bsky.social review, we discuss how phase separation, avidity, and wetting shape autophagy at the molecular level.
Great collaboration with @wilflinglab.bsky.social
www.cell.com/trends/bioch...
In our new @cp-trendsbiochem.bsky.social review, we discuss how phase separation, avidity, and wetting shape autophagy at the molecular level.
Great collaboration with @wilflinglab.bsky.social
www.cell.com/trends/bioch...
Autophagy regulation by phase separation, avidity, and wetting
Autophagy enables cells to selectively degrade a wide range of macromolecules, and
how this process achieves spatial precision within the densely packed cytosol is an
active area of investigation. Rec...
www.cell.com
November 20, 2025 at 10:10 PM
Yes was absolute fun! Like always a fantastic collaboration.
Reposted by Wilfling Lab
🔄 Repost because the previous link was broken! To degrade or not to degrade! We put together an Autophagic Punctum with @wilflinglab.bsky.social on our latest paper, take a look if you're interested!
🔗 www.tandfonline.com/doi/full/10....
🔗 www.tandfonline.com/doi/full/10....
To degrade or not to degrade: how phase separation modulates selective autophagy
Selective macroautophagy/autophagy relies on newly formed double-membrane compartments, known as phagophores, to sequester and recycle diverse cellular components, including organelles, biomolecula...
www.tandfonline.com
March 12, 2025 at 12:31 PM
🔄 Repost because the previous link was broken! To degrade or not to degrade! We put together an Autophagic Punctum with @wilflinglab.bsky.social on our latest paper, take a look if you're interested!
🔗 www.tandfonline.com/doi/full/10....
🔗 www.tandfonline.com/doi/full/10....
Looking forward to this fantastic meeting!
⌛️7 days left for registration: ➡️ www.ubiquitin-wuerzburg-2025.de ⬅️
…and on we go with proteostasis - warm welcome to our autophagy researchers Anja Bremm from @goetheuni.bsky.social and @wilflinglab.bsky.social!
#WUeBI2025 #ubiquitin #autophagy
…and on we go with proteostasis - warm welcome to our autophagy researchers Anja Bremm from @goetheuni.bsky.social and @wilflinglab.bsky.social!
#WUeBI2025 #ubiquitin #autophagy
February 22, 2025 at 7:27 PM
Looking forward to this fantastic meeting!
Reposted by Wilfling Lab
🚨 Paper Alert! We’re starting off the year with our latest publication in @naturecellbiology.bsky.social on the role of phase separation in selective autophagy initiation!
This work was a close and exciting collaboration with
@wilflinglab.bsky.social
🔗 nature.com/articles/s41...
Here's a thread👇
This work was a close and exciting collaboration with
@wilflinglab.bsky.social
🔗 nature.com/articles/s41...
Here's a thread👇
Phase separation of initiation hubs on cargo is a trigger switch for selective autophagy - Nature Cell Biology
Licheva, Pflaum, Babic, Mancilla et al. show that low-affinity cargo–receptor interactions promote autophagy receptor mobility and condensation of the scaffold protein Atg11 to trigger initiation hub ...
nature.com
January 7, 2025 at 10:30 AM
🚨 Paper Alert! We’re starting off the year with our latest publication in @naturecellbiology.bsky.social on the role of phase separation in selective autophagy initiation!
This work was a close and exciting collaboration with
@wilflinglab.bsky.social
🔗 nature.com/articles/s41...
Here's a thread👇
This work was a close and exciting collaboration with
@wilflinglab.bsky.social
🔗 nature.com/articles/s41...
Here's a thread👇
Thanks to all collaborators, a fantastic collaboration with the @kraftlabfr.bsky.social, several fun retreats & a special thanks to the first authors Mariya, Jeremy, @riccardobabic.bsky.social, and @heaktor.bsky.social
January 8, 2025 at 3:11 PM
Thanks to all collaborators, a fantastic collaboration with the @kraftlabfr.bsky.social, several fun retreats & a special thanks to the first authors Mariya, Jeremy, @riccardobabic.bsky.social, and @heaktor.bsky.social
Our study provides insights into the process of initiation during selective autophagy and offers new ideas for developing approaches to selectively degrade unwanted cellular material by autophagy.
January 8, 2025 at 3:11 PM
Our study provides insights into the process of initiation during selective autophagy and offers new ideas for developing approaches to selectively degrade unwanted cellular material by autophagy.
3) Experiments using mammalian cell systems reveal striking similarities where FIP200 (Atg11 homologue) clusters on the cargo surface, connecting the phagophore assembly site to the ER. Changing receptor affinity of p62 within condensates resulted in a degradation defect similar to yeast.
January 8, 2025 at 3:11 PM
3) Experiments using mammalian cell systems reveal striking similarities where FIP200 (Atg11 homologue) clusters on the cargo surface, connecting the phagophore assembly site to the ER. Changing receptor affinity of p62 within condensates resulted in a degradation defect similar to yeast.
2) The low affinity of the receptor for the cargo also allows the initiation hubs to rearrange and establish organelle contact sites necessary to form the pre-autophagosomal structure. Reconstitution of these features allowed us to transform a viral protein expressed in yeast into a neo-cargo.
January 8, 2025 at 3:11 PM
2) The low affinity of the receptor for the cargo also allows the initiation hubs to rearrange and establish organelle contact sites necessary to form the pre-autophagosomal structure. Reconstitution of these features allowed us to transform a viral protein expressed in yeast into a neo-cargo.
1) These low affinity interactions are important for the formation of Atg11 condensates at the cargo surface. Atg11 condensates act as initiation hubs to recruit core autophagy machinery proteins such as Atg1 and Atg9.
January 8, 2025 at 3:11 PM
1) These low affinity interactions are important for the formation of Atg11 condensates at the cargo surface. Atg11 condensates act as initiation hubs to recruit core autophagy machinery proteins such as Atg1 and Atg9.
What happens if you change the physical properties of an autophagic cargo? By altering the low-affinity interaction of autophagic receptors with or within their cargo, we observed a severe degradation defect in budding yeast.
January 8, 2025 at 3:11 PM
What happens if you change the physical properties of an autophagic cargo? By altering the low-affinity interaction of autophagic receptors with or within their cargo, we observed a severe degradation defect in budding yeast.
Check out our latest publication in @naturecellbiology.bsky.social on the role of phase separation in selective autophagy initiation! This was done in a fantastic collaboration with
@kraftlabfr.bsky.social
www.nature.com/articles/s41...
Short teaser below 👇👇👇
@kraftlabfr.bsky.social
www.nature.com/articles/s41...
Short teaser below 👇👇👇
Phase separation of initiation hubs on cargo is a trigger switch for selective autophagy - Nature Cell Biology
Licheva, Pflaum, Babic, Mancilla et al. show that low-affinity cargo–receptor interactions promote autophagy receptor mobility and condensation of the scaffold protein Atg11 to trigger initiation hub ...
www.nature.com
January 8, 2025 at 3:11 PM
Check out our latest publication in @naturecellbiology.bsky.social on the role of phase separation in selective autophagy initiation! This was done in a fantastic collaboration with
@kraftlabfr.bsky.social
www.nature.com/articles/s41...
Short teaser below 👇👇👇
@kraftlabfr.bsky.social
www.nature.com/articles/s41...
Short teaser below 👇👇👇
Great opportunity! We are looking for a PhD student to work on novel sample preparation methods for cryo-electron tomography.
Are you already on track to apply to our #gradschool? 👣 This is a little map of our application process! We hope, you don´t get lost on the way 😊
If you want to start your #phdjourney with IMPRS-CBP #applynow
Don’t miss the chance and apply by February 7th.
👉 imprs-cbp.mpg.de 👈
#imprs_cbp
If you want to start your #phdjourney with IMPRS-CBP #applynow
Don’t miss the chance and apply by February 7th.
👉 imprs-cbp.mpg.de 👈
#imprs_cbp
December 11, 2024 at 10:41 PM
Great opportunity! We are looking for a PhD student to work on novel sample preparation methods for cryo-electron tomography.
Congrats Mariana!
December 3, 2024 at 9:01 PM
Congrats Mariana!
Humbled and excited to join the EMBO young investigator community. Congratulations to all and looking forward to meeting you in the future.
www.embo.org/press-releas...
www.embo.org/press-releas...
Twenty-seven scientists become EMBO Young Investigators – Press releases – EMBO
The group leaders join an international network of nearly 800 life scientists and receive financial support
www.embo.org
December 3, 2024 at 8:23 PM
Humbled and excited to join the EMBO young investigator community. Congratulations to all and looking forward to meeting you in the future.
www.embo.org/press-releas...
www.embo.org/press-releas...
I am humbled to be a part of this amazing community. Thanks to the entire group, including fantastic colleagues and mentors along the way.
December 3, 2024 at 7:54 PM
I am humbled to be a part of this amazing community. Thanks to the entire group, including fantastic colleagues and mentors along the way.