Jason Cantor

PEX39 facilitates the peroxisomal import of PTS2-containing proteins - Nature Cell Biology Chen et al. show that PEX39 cooperates with PEX7 in the peroxisomal import of proteins containing a PTS2 site and uncover an (R/K)PWE motif in PEX39 and PEX13 that binds to PEX7 and facilitates the im...

Our work on new paradigm in peroxisome biogenesis and PEX39 (1st human peroxisomal biogenesis protein (peroxin/PEX) found in > 20 yr) is out in @natcellbio.nature.com! Equal collab w/Tony Rodrigues (Jorge Azevedo lab), @dwendscheck.bsky.social (Bettina Warscheid lab)

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

big congrats, my friend, awesome work! 🎉

Super excited to share new review on metabolic stress and adaptations in pancreatic cancer to these stresses from @cssheehan.bsky.social
jci.org/articles/vie... 1/6

Engineered reactivity of a bacterial E1-like enzyme enables ATP-driven modification of protein and peptide C termini Nature Chemistry - In living systems, ATP provides an energetic driving force for protein synthesis and modification. Now, an engineered enzymatic tool has been developed for high-yield, ATP-driven...

Excited to share our latest: we engineered the reactivity of a bacterial E1-like enzyme for ATP-driven modification of C termini. Our tool mimics the logic of peptide bond formation in biology for precision modification of proteins in vitro. 🧪https://rdcu.be/ewN7C

congrats, Walter!!

Congrats to you and your team, Natalie!!

Mitochondrial presequences harbor variable strengths to maintain organellar function Hundreds of mitochondrial-destined proteins rely on N-terminal presequences for organellar targeting and import. While generally described as positively charged amphipathic helices, presequences lack ...

Very excited to share our latest work, “Mitochondrial presequences harbor variable strengths to maintain organellar function,” led by the fantastically talented @washubbsb.bsky.social graduate student Youmian Yan. A 🧵

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

Cytosolic NADK is conditionally essential for folate-dependent nucleotide synthesis Nature Metabolism, Published online: 02 May 2025; doi:10.1038/s42255-025-01272-3In this study, Flickinger et al. uncover the essential role of cytosolic NADK and why the relative importance of this role further depends on folate availability.

ICYMI:

a penguin is reading a book while sitting on a pile of books reading vibes ALT: a penguin is reading a book while sitting on a pile of books reading vibes

Good Sunday, all. Here is a summary of papers in #cancermetabolism and #mitochondrialbiology, packed with superexciting science and discoveries. Don't miss it, check it here: biomed.news/bims-camemi/... @biomednews.bsky.social

"Love is the quality of attention we pay to things."
-J. D. McClatchy

...as secreted by millions of other cells in the population. our prior screen data, at least, suggested that NADK2 was diff. essential in DMEM v. HPLM or RPMI regardless of FBS dialysis, though we also often use relatively lower seeding density, etc. just some speculation at least, great q! 4/4

...so, in the context of a pooled population as is the basis of pooled CRISPR screens, it is certainly possible (if not likely) that based on seeding density and passaging frequency used thru the screen duration, the NADK2-KO cells within the population may indeed be exposed to exogenous Pro...3/n

...also possibly just an artifactual consequence of technical parameters used for specific CRISPR screens in 'batch' format (though often not reported). we and others have seen that in some cases, cultured cells 'net secrete' Pro into exogenous media over time...2/n

thanks so much, Dylan!! great q! edited for clarity :)
1-for the screens carried out in RPMI, this would certainly seem to be the case (there is plenty of exogenous Pro around)
2-for those in DMEM, it may be that 'standard' 10-20% FBS provides ample Pro...but...1/n

thanks so much, Christian!! 🙏

thanks, Iza - hope that all is well!!

thank you, my friend!! 🙏

thanks, Natalie!! 🎉

thank you, Tim!!

thanks so much, Alex!! 😀

armed with his metabolism background, Kyle will now go on to pursue his postdoc exploring regen bio w/Ken Poss, while we continue our ongoing efforts to unravel mechanistic insights into conditional gene essentiality among other directions! 11/11

nonetheless, our findings indicate that selective NADK inhibitors may be leveraged to effectively slow DHFR activity, impairing cell growth while eluding resistance mechanisms related to direct DHFR inhibitors such as methotrexate...10/n

given the central role of NADPH in several processes, it comes as no surprise that NADK has garnered attention as a possible target for cancer therapy, but using NADK-KO cells, we corroborate that TN (deemed a lead compound against NADK) elicits off-target effects...9/n

this finding also complements a distinct gene-nutrient interaction between the mitochondrial NADK2 and proline that was uncovered a few years ago by both Craig Thompson &
Gerta Hoxhaj (who has generated tons of beautiful work in this space overall) 8/n

ultimately, we find that NADK is required to support cytosolic/NADPH-driven DHFR activity sufficient to maintain the de novo synthesis of thymidylate and purines in low folic acid conditions – effectively explaining why NADK dependence can vary based on nutrient conditions... 7/n

this gene–nutrient interaction likely clarifies why NADK dependence has been masked at least in part across nearly all cataloged CRISPR screens carried out in traditional media...6/n

we previously identified NADK as a selectively essential gene for cells in HPLM v RPMI. here, we traced this conditional phenotype to the differential availability of folic acid, a key vitamin included at highly supraphysiologic levels in RPMI and other classic media. 5/n

NAD kinase essentiality in cancer: in real life, it is all about folates - Nature Metabolism NAD kinases have a crucial role in the de novo synthesis of the cofactor NADP+ by phosphorylating NAD+ to yield NADP+. A study by Flickinger et al. uses physiologically relevant cell culture media wit...

finally, thanks to @meiserlab.bsky.social for the beautiful accompanying N&V! tinyurl.com/esvjxw2 4/n

we are very grateful to the several funding sources that made this study possible, esp @americancancersoc.bsky.social
and the NIH! a big thanks to Alfredo for leading an extremely helpful and productive review process and to our reviewers for their thoughtful comments! 3/n

…and a big thanks to our awesome collaborators
@judisimcox.bsky.social & Gina for their contributions and expertise in lipidomics, and to Kathryn from the UWCCC
flow cytometry lab for invaluable help and advice! 2/n

huge congrats to first author @kyle-flickinger.bsky.social, who drove this study as the major component of his PhD thesis & in the process became our resident expert in folate/1C metabolism! also grateful for contributions from @carlosmf.bsky.social @thebiokimist.bsky.social, Gavin…1/n