Wilfling Lab

Wilfling Lab

@wilflinglab.bsky.social

Investigating mechanisms of eukaryotic cellular quality control with a focus on autophagy @MPIbp via #cryoET, #teamtomo, #cellbiology and #massspectrometry

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Wilfling Lab
@wilflinglab.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

Wilfling Lab reposted

David Teis
@teislab.bsky.social

Fantastic collaboration with @wilflinglab.bsky.social Cunqi Ye & Benoît Kornmann www.biorxiv.org/content/10.6...

biorxiv.orgbiorxiv.org
David Teis@teislab.bsky.social

We found that cells survive a proteostasis defect, but not the lipid imbalance it causes. Rer1 & the Dsc complex triage orphan membrane proteins at the Golgi. Lose both & DAG-rich multilamellar compartments (DMCs) form. Drain DAG & cellular architecture recovers. www.biorxiv.org/content/10.6...

Wilfling Lab reposted

Felix Kraus
@sauerkrausi.bsky.social

Happy to share our neuronal lysosomal storage disorder toolkit has been published in PNAS! 📚Paper: www.pnas.org/doi/10.1073/...

pnas.orgPNASProceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...
Felix Kraus@sauerkrausi.bsky.social

Updated preprint 🧵 We mapped how loss of 23 LSD genes reshapes neuronal proteomes in cortical (iN) and dopaminergic (iDA) neurons New in v2: We added a computational PPI pipeline assessing KO-dependent vulnerability at the interaction and complex level.

Wilfling Lab reposted

Felix Kraus
@sauerkrausi.bsky.social

Updated preprint 🧵 We mapped how loss of 23 LSD genes reshapes neuronal proteomes in cortical (iN) and dopaminergic (iDA) neurons New in v2: We added a computational PPI pipeline assessing KO-dependent vulnerability at the interaction and complex level.

Wilfling Lab
@wilflinglab.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

Wilfling Lab
@wilflinglab.bsky.social

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.orgCathepsin C–Catalyzed Ligation Generates Intralysosomal Amyloid Fibrils from Dipeptide EstersAmyloid 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
Wilfling Lab
@wilflinglab.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

Wilfling Lab
@wilflinglab.bsky.social

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.

Wilfling Lab
@wilflinglab.bsky.social

Yes was absolute fun! Like always a fantastic collaboration.

Claudine Kraft's Lab @kraftlabfr.bsky.social

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...

cell.comAutophagy regulation by phase separation, avidity, and wettingAutophagy 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...

Wilfling Lab reposted

Claudine Kraft's Lab
@kraftlabfr.bsky.social

🔄 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....

tandfonline.comTo degrade or not to degrade: how phase separation modulates selective autophagySelective macroautophagy/autophagy relies on newly formed double-membrane compartments, known as phagophores, to sequester and recycle diverse cellular components, including organelles, biomolecula...
Wilfling Lab
@wilflinglab.bsky.social

Looking forward to this fantastic meeting!

GRK2243@grk2243.bsky.social

⌛️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

Wilfling Lab reposted

Claudine Kraft's Lab
@kraftlabfr.bsky.social

🚨 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👇

nature.comPhase separation of initiation hubs on cargo is a trigger switch for selective autophagy - Nature Cell BiologyLicheva, 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 ...
Wilfling Lab
@wilflinglab.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.

Wilfling Lab
@wilflinglab.bsky.social

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.

Wilfling Lab
@wilflinglab.bsky.social

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.

Wilfling Lab
@wilflinglab.bsky.social

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.

Wilfling Lab
@wilflinglab.bsky.social

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.

Wilfling Lab
@wilflinglab.bsky.social

Great opportunity! We are looking for a PhD student to work on novel sample preparation methods for cryo-electron tomography.

IMPRS on Cellular Biophysics@imprs-cbp.bsky.social

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

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