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/...

Could oddly behaving mitochondria hold the key to treating leukaemia? - Futurum Dr Kelsey Fisher-Wellman is comparing mitochondria in healthy and cancerous cells so that treatments for leukaemia can target these differences.

futurumcareers.com/cancer-biolo...

Ruben Mesa: An Amazing Cancer Biology Department Driving Advances Across Advocate Health - OncoDaily Ruben Mesa: An Amazing Cancer Biology Department Driving Advances Across Advocate Health / advocate health, Atrium Health, cancer, cancer biology, OncoDaily,

An Amazing Cancer Biology Department Driving Advances Across Advocate Health - Ruben Mesa

@rubenmesamd.bsky.social

oncodaily.com/blog/ruben-m...

#OncoDaily #Oncology #Cancer #Health #Medicine #MedEd #MedOnc #MedNews

The negative impact of α-ketoglutarate dehydrogenase complex deficiency on matrix substrate-level phosphorylation A decline in α-ketoglutarate dehydrogenase complex (KGDHC) activity has been associated with neurodegeneration. Provision of succinyl-CoA by KGDHC is essential for generation of matrix ATP (or GTP) by...

Some caution around isolated enzyme experiments, I love this example:
SUCL activity is due to succinyl-CoA production from AKGDH. Thus you can genetically down regulate AKGDH, isolate mitochondria and test maximal SUCL activity and see no difference.
pmc.ncbi.nlm.nih.gov/articles/PMC...

Thank you for the shout-out, Dr. Kridel!

Quite an essay on the basis of cancer entitled "The End of the Genetic Paradigm of Cancer" @plosbiology.org arguing against the primacy of somatic mutations (traditional model) and cells, invoking gene regulatory networks and tissue
journals.plos.org/plosbiology/...

1/For over a decade, we’ve been studying tumor metabolism in patients with non-small cell lung cancer

This long-term commitment allowed us to connect tumor metabolic features to patient outcomes

We found that 13C glucose contribution to the TCA cycle predicts overall survival in NSCLC

Oh no...I had no idea it was about mitos.
Originally talked myself out of reading, now this fellow mitochondrial researcher might have to

A great talk from Navdeep Chandel today at the Molecular and Cellular Oncology (MCO) retreat for the Comprehensive Cancer Center today. All things #mitochondria in #cancer and other diseases. Great talks from all the other faculty as well.
@rubenmesamd.bsky.social
🐪🏙️🦀🧬

Also, very clear around minute 27 — with aberrant PIK3-mut signalling, you lose resolution of where that signal is going. It is harder to distinguish, and you blur the lines of the signal distribution.

While fundamental, gene expression & signalling pathways are often oversimplified, especially, in the oncological context. Outputs are probabilistic, not deterministic. Not an off/on switch, but broadening and heterogeneity of the amplified signal.
www.youtube.com/watch?v=WiJo...

DNMT3AR882H Is Not Required for Disease Maintenance in Primary Human AML, but Is Associated With Increased Leukemia Stem Cell Frequency Genetic mutations are being thoroughly mapped in human cancers, yet a fundamental question in cancer biology is whether such mutations are functionally required for cancer initiation, maintenance of e...

DNMT3A mutations were dispensable for AML maintenance. Replacing mutants with wild-type did not impair engraftment. DNMT3A mutations are necessary for AML initiation, but dispensable for disease maintenance. Initiating oncogenes differ from maintenance.
www.biorxiv.org/content/10.1...

Clear and comprehensive new go-to review from #NoTwitterNav (we're gonna need a new hashtag) delineating how mitochondria have distinct and context-specific roles in proliferation and fate determination www.annualreviews.org/content/jour...

Pharmacologically targetable vulnerability in prostate cancer carrying RB1-SUCLA2 deletion - Oncogene Oncogene - Pharmacologically targetable vulnerability in prostate cancer carrying RB1-SUCLA2 deletion

Diving into mSLP for part of my PhD.

Discussed here, and in other papers (even back to 2004), SUCLA2 and SUCLG2 are not interchangeable and can lack compensatory activity for one another. This fact is lost in many textbooks & graphical depictions of the TCA cycle.

Looks like it is time for an attempt to rebuild on this platform! 🙏