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Good Sunday, all! Here is the curated weekly collection of papers in #cancermetabolism and #mitochondrialbiology. Don't miss it; find it here: biomed.news/bims-camemi/... Biomed News #keepreading
"It's very simple to be happy. But it's very difficult to be simple." - Rabindranath Tagore
Latest collection of papers on mitochondria in health and disease! #MitochondrialDisease #week3
biomed.news/bims-mitdis/...
@biomednews.bsky.social @gavinmcstay.bsky.social @mitoscientist.bsky.social @mitoscientists.bsky.social
www.nature.com/articles/s42...
thank you, my friend!
thank you, Ci Ji!
thanks for the kind words, Scott!
🙏 We would also like to thank Alfredo, Yanina, Christoph Schmitt, & the @natmetabolism.nature.com team for an extremely helpful and productive review process, and to our reviewers for their thoughtful comments & suggestions! 12/12
🙏 Special thanks to @acscan.bsky.social for their investment in this study and their continued support of our research! 11/n
...to Kyle Flickinger, who spearheaded several key experiments last summer, and our entire team of co-authors and collaborators! 10/n
Huge congrats to @thebiokimist.bsky.social, whose rare blend of motivation, creativity, & resilience drove this story and will certainly propel her toward continued success (now a clinical fellow at WashU!)...9/n
This study further illustrates that using HPLM isn't just about modeling the body and showing that cells behave "differently" vs. the classic media that have been around for 50+ years - it can be a powerful lens for uncovering new mechanistic biology. 8/n
...Glucose capture (OMM-detached HK), commitment to glycolysis (PFK1), and proton-coupled lactate efflux (MCT) - largely in line with elegant work from the Rabinowitz lab derived from using a completely orthogonal system/approach. 7/n
We further found that MCT4 (SLC16A3) expression can predict (conditional) HK2 dependence. By leveraging our CRISPR screen data, we further propose that the Warburg effect is driven by 3 steps...6/n
Ultimately, in contrast to these debated explanations, our data suggest OMM-detached HK supports glycolytic ATP production, which we propose is compartmentalized to meet the energetic demands of essential processes in close proximity. 5/n
Given this link, we decided to use conditional HK2 essentiality as a metabolic probe to interrogate several proposed theories to explain the benefit of Warburg metabolism. 4/n
Contrary to traditional theories, we found that HK detachment from the mitochondria actually supports both cell growth and aerobic glycolysis ("the Warburg effect") 3/n
Both contain a short N-terminal domain, which facilitates association w/ the outer mitochondrial membrane (OMM). However, HK1 was dispensable for cell growth in our screens, and notably, both HK1/2 were defined as "essential" in a negligible fraction of the ~1,200 cell lines in DepMap. 2/n
Using CRISPR screens, we had previously identified hexokinase 2 (HK2) as a selectively essential gene for cells grown in HPLM versus conventional RPMI. Most cancer cells express two highly homologous HK isoforms (HK1 & HK2) 1/n
For ~century, we’ve asked: why do proliferating cells ferment glucose even when O2 is around? I’m thrilled to share our latest work @natmetabolism.nature.com, led by @thebiokimist.bsky.social. By leveraging conditional essentiality in HPLM, we propose a provocative new answer to this classic Q. 🧵
Really thrilled to have our work on mitochondrial presequence strength out today @jcb.org. We establish quantitative parameters to better define "strong" and "weak" presequences both in vitro and in vivo. This work was spearheaded by the ever talented Youmian Yan, a BBSB graduate student in my lab.
thank you, my friend!
happy to have collaborated on this v cool study led by Andy & Aaron from the Sean Palecek and Melissa Skala labs! culturing hPSC-CMs in HPLM effectively enhances their maturation vs traditional media ➡️ potential modeling implications for cardiac biology/CVD!
tinyurl.com/3yutyd8c
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...
!
Super excited to share our new preprint from @cssheehan.bsky.social on how the tumor microenvironment causes drug resistance in pancreatic cancer: www.biorxiv.org/content/10.1...
Position-specific frequency matrices can be used to calculate z-scores comparing enzyme-treated and control samples. The z-scores are plotted as heatmaps that represent an enzyme specificity profile.
New preprint: we developed a method that uses phosphoproteome-derived peptide libraries (PhosPropels) for deep specificity profiling of phosphatases and phospholyases www.biorxiv.org/content/10.1...
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
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!!
