Aakriti Jain

Excited to share our work @nature.com! Postdoc @mariopalma.bsky.social, with major contributions from @retickerflynn.bsky.social and collaborators, discovered melanoma cells in lymph nodes gain a targetable FSP1 dependency that limits progression. #TeamFSP1

www.nature.com/articles/s41...

NUDT5 regulates purine metabolism and thiopurine sensitivity by interacting with PPAT Cells generate purine nucleotides through de novo purine biosynthesis (DNPB) and purine salvage. Purine salvage represses DNPB to prevent excessive purine nucleotide synthesis through mechanisms that ...

1/New paper from Zheng Wu, Phong Nguyen et al. @cri-utsw.bsky.social shows how cells balance the two pathways that produce purine nucleotides: de novo purine biosynthesis (DNPB) and purine salvage. The surprising mechanism involves NUDT5, a Nudix hydrolase

www.science.org/doi/10.1126/...

FSP1-mediated lipid droplet quality control prevents neutral lipid peroxidation and ferroptosis - Nature Cell Biology Lange et al. identify a lipid droplet quality control pathway in which FSP1 safeguards stored neutral lipids from lipid peroxidation, thereby preventing the induction of ferroptosis.

Excited to share my postdoc work @olzmannlab.bsky.social! We found lipid droplets, the cell’s lipid storage depots, are subject to oxidative damage and are protected by FSP1. Loss of FSP1 triggers droplet peroxidation and cell death, revealing a new layer of lipid quality control!

shorturl.at/B5XYD

Accumulation of succinate suppresses de novo purine synthesis through succinylation-mediated control of the mitochondrial folate cycle The de novo purine synthesis pathway is fundamental for nucleotide production, yet the role of mitochondrial metabolism in modulating this process rem…

Excited to share our latest work out today in @cp-molcell.bsky.social, revealing a molecular link between succinate dehydrogenase and purine synthesis, connecting two fundamental metabolic pathways. Huge congratulations to the first author, Mushtaq Nengroo! www.sciencedirect.com/science/arti...
!

Thrilled to announce the launch of my lab
@cri-utsw.bsky.social at UTSW this January!

We will explore how cells sense and respond to mechanical forces, focusing on membrane mechanics to reveal how tension and signaling work together to shape cell behavior.

Congrats James!! 🥳🥳

Vitamin B2 metabolism promotes FSP1 stability to prevent ferroptosis Ferroptosis, a regulated form of cell death driven by excessive lipid peroxidation, has emerged as a promising therapeutic target in cancer. Ferroptosis suppressor protein 1 (FSP1) is a critical regul...

Excited to share our new preprint, led by Kirandeep Deol! 🤩 Genetic screens uncover mechanisms regulating FSP1 abundance in cancer. Vitamin B2 metabolism promotes FSP1 stability via FAD synth / binding, further linking nutrient metabolism to ferroptosis.
www.biorxiv.org/content/10.1...

Multi-scale Molecular Imaging of Human Cells reveals COPI and COPII Vesicles at ER Exit Sites Trafficking from the endoplasmic reticulum to the Golgi apparatus comprises the first steps toward the correct localization of 30% of eukaryotic proteins. Coat protein complexes COPII and COPI are inv...

Go check out the latest preprint from Giulia Zanetti's lab. @dr-downes.bsky.social used cryo-tomography to directly visualize COPI and COPII coated vesicles in situ at unprecedented resolution in human cells. Amazingly beautiful, rigorous, insightful work.
www.biorxiv.org/content/10.1...

And it's out!

I'm thrilled to share our new paper (Adriaenssens et al., Nat Cell Biol 2025).

This paper describes a new mechanism for the initiation of autophagosome biogenesis.

We found that this WIPI-ATG13-driven pathway is preferentially used by a group of transmembrane autophagy receptors.

The role of metabolism in shaping enzyme structures over 400 million years - Nature By combining structural biology and evolutionary genomics analyses, the evolution of enzymes over 400 million years is shown to be governed by catalytic function, metabolic network architecture, cost ...

A paper I have been working on with Oliver Lemke in the Ralser lab has just come out: www.nature.com/articles/s41...

We used predicted structures to gain insight into the evolution of metabolic proteins in yeast.

A bit more in this linked-in post (www.linkedin.com/posts/benjam...).

Beautiful beautiful story and we love a mass spec imaging start leading to a lysosome dependent mechanism!! 😍

We’re excited to share a new pre-print from the lab! Led by Carmen Ramirez Moncayo and a fantastic collaboration with several groups from across @mrc-lms.bsky.social & @imperialcollegeldn.bsky.social. Interested in #OvarianCancer, #PARPinhibitors or #DrugDistribution? please read on! bit.ly/45lpekS

JIP4 deficiency causes a novel lysosome storage disease arising from impaired cystine efflux Lysosomes break down macromolecules, clear cellular waste and recycle nutrients such as cystine. We describe a novel mechanism whereby JIP4 regulates lysosomal cystine storage by controlling the abundance of cystinosin (CTNS), the transporter responsible for lysosomal cystine efflux. To this end, JIP4, previously characterized as a motor adaptor and kinase signaling scaffold, suppresses TMEM55B-dependent ubiquitylation of CTNS. Loss of JIP4 reduces CTNS protein levels, leading to lysosomal cystine accumulation and lysosomal storage defects that phenocopy loss of CTNS in both human cells and the renal proximal tubules of JIP4 knockout mice. These phenotypes mirror cystinosis, the lysosomal storage disease caused by CTNS loss-of-function. Our findings thus reveal a fundamental process that controls the efflux of lysosomal cystine and has relevance to understanding human disease arising from JIP4 mutations. ### Competing Interest Statement The authors have declared no competing interest. NIH, AG085824, AG062210, R35GM150619 Michael J. Fox Foundation, https://ror.org/03arq3225, ASAP-000580

I am excited to share our new preprint! Led by @laylanassar.bsky.social , we have found a new JIP4-dependent mechanism that controls the efflux of cystine from lysosomes. Our findings have implications for both lysosome biology and human disease: doi.org/10.1101/2025...

ATG9A and ARFIP2 cooperate to control PI4P levels for lysosomal repair Lysosome damage activates multiple pathways to prevent lysosome-dependent cell death, including a repair mechanism involving endoplasmic reticulum (ER…

*ATG9A alert*👀👀

Curious about how ATG9A maintains lysosomal homeostasis via PI4P? Check out the new work from my postdoc in @satooze.bsky.social lab.
Thrilled to see this finally published!
Special thanks to @ealmacellas.bsky.social

www.sciencedirect.com/science/arti...

Only purifying fluorescently tagged proteins from now on - look at those beautiful mcherry fused proteins 😍💜

Cocrystal structure reveals the mechanism of FSP1 inhibition by FSEN1 | PNAS FSP1 is an FAD-dependent oxidoreductase that uses NAD(P)H to regenerate the reduced forms of lipophilic quinone antioxidants, such as coenzyme Q10 ...

Thrilled this paper is out! We solved the first cocrystal structure of FSP1 with an inhibitor (FSEN1), providing mechanistic insight & a foundation for medchem. Led by Amalia Megarioti & Sitao Zhang. A terrific collaboration with Da Jia.
Brief Skytorial!
1/9

EndoMAP.v1 charts the structural landscape of human early endosome complexes - Nature A study presents EndoMAP.v1, a resource that combines information on protein interactions and crosslink-supported structural predictions to map the interaction landscape of early endosomes.

New work @harvard by Miguel Gonzalez-Lozano @harperlabhms.bsky.social & @ernstschmid.bsky.social in Johannes Walter lab charts structural interactome of endosomes. #XL-MS #Alphafold Funded by @asapresearch.parkinsonsroadmap.org & NIH. Science continues-despite attacks www.nature.com/articles/s41...

So exciting to see this out!!

Online today in @nature.com - our latest study led by superstar postdoc Gilles Rademaker detailing the role of PSCK9 in driving sterol dependent metastatic organ choice in pancreatic cancer nature.com/articles/s41...
full text available here 👉 rdcu.be/em0VG and thread 👇

Cryo-EM structure of CASTOR1-GATOR2 complex

mTORC1 is activated when cells are fed with amino acids. New preprint with @robzonculab.bsky.social led by Rachel Jansen shows how the massive "CastiGATOR" complex is formed when arginine-free CASTOR1 binds to the GATOR2 complex to antagonize mTORC1 starved cells. tinyurl.com/yr6en6f4

LRP10 promotes trafficking of progranulin and prosaposin to lysosomes Mutations in LRP10, a low-density lipoprotein receptor family member, cause familial Parkinson's disease and dementia with Lewy bodies. However, its direct cellular functions remain largely undefined....

Here’s a new set of discoveries led by Francesca Filippini: doi.org/10.1101/2025...
We found that LRP10 promotes the efficient delivery of progranulin to lysosomes and that microglia are particularly sensitive to loss of LRP10.

The nitroplast: A nitrogen-fixing organelle A bacterial endosymbiont of marine algae evolved to an organelle

Move over mitochondria, a new organelle called the nitroplast is here.

In a Science study last year, researchers reported that a nitrogen-fixing organelle has been identified in a marine alga.

Learn more in this #SciencePerspective: scim.ag/49GjClc #ScienceMagArchives

Our PKA-autophagy story by outstanding graduate student Ashley Segura (co-led with Rose Citron) published in @embojournal.org, dissects a deep connection between autophagy and PKA in neuronal signaling, with implications for neurological disease. Great collaboration with @manciaslab.bsky.social!

Happy to share the first paper in my PhD is published in JCB!
It's my honor to work with amazing teammates! I really enjoy exploring mitochondrial protein import mechanism through cryo-ET!

Rapid optimization of protein function in mammalian cells via microbe-independent deep assembly and screening Random mutagenesis and deep mutational scanning (DMS) are widely used to optimize proteins by oversampling large libraries in microbial cells, selecting cells expressing favorable variants, and sequen...

Despite daily disruptions, scientists try to use logic and creativity to help fellow humans.

Thus I would like to report our latest work describing microbial-independent deep assembly and screening, a method that goes from primers to mammalian cell assays in 1 day.

www.biorxiv.org/content/10.1...

Cell membranes sustain phospholipid imbalance via cholesterol asymmetry This work challenges a major assumption in cell biology by showing that lipid bilayers can have drastically different phospholipid abundances between their two leaflets. This lipid abundance asymmetry...

Groundbreaking study in Cell from @leventallab.bsky.social: phospholipid asymmetry is a defining feature of the plasma membrane and cholesterol fills the holes — major implications for how this membrane works. A #lipidtime must-read! www.cell.com/cell/abstrac...

Tissue-like multicellular development triggered by mechanical compression in archaea The advent of clonal multicellularity is a critical evolutionary milestone, seen often in eukaryotes, rarely in bacteria, and only once in archaea. We show that uniaxial compression induces clonal mul...

Striking new study from @archaeon-alex.bsky.social's lab just out in @science.org on multicellular development induced by compression in Archaea: www.science.org/doi/10.1126/...

Exciting discovery by Aakriti Jain @aakritijain.bsky.social et al of the @robzonculab.bsky.social lab that LyLAP processively and rapidly proteolyses membrane-spanning hydrophobic domains of transmembrane proteins!

Thank you prasanna!

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...

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/...