10/ If you’re interested in cancer metabolism, FAO biology, or isotope tracing, we’d love your thoughts, questions, and critiques on this v2.
Preprint (open access):
www.biorxiv.org/content/10.1...
9/ Conceptually, this work:
Separates FAO capacity from FAO contribution
Highlights the importance of multi-fuel integration (fatty acids + glutamine + glucose)
Provides a quantitative framework to reinterpret FAO-targeted therapies
8/ Why does this matter?
Because it reframes how we think about FAO inhibitors in cancer.
Their efficacy may stem less from “starving” tumours of calories, and more from disrupting this flexible acetyl‑CoA support system.
7/ This challenges the prevailing idea that FAO is a primary bioenergetic fuel in cancer.
Instead, FAO looks like a compensatory rheostat: more about topping up acetyl‑CoA under glucose limitation than about bulk ATP production.
6/ Mechanistically, FAO works together with glutamine metabolism via a malic enzyme–dependent shunt.
This combination sustains acetyl‑CoA while preserving glucose-derived anaplerotic flux into the TCA cycle, rather than displacing glucose oxidation.
5/ If fat is not the main mitochondrial fuel, what is FAO doing?
We find FAO behaves more like a backup system: it helps maintain the mitochondrial acetyl‑CoA pool when glucose-derived acetyl‑CoA is limited.
4/ FAO capacity varied more than 8-fold across the panel.
Yet exogenous long-chain fatty acids consistently contributed <10% of carbon to TCA cycle intermediates in every single cell line.
So high FAO ≠ high fat contribution to mitochondrial carbon.
3/ We profiled 27 cancer cell lines using parallel stable-isotope tracing plus metabolic phenotyping to quantify both FAO capacity and carbon entry into the TCA cycle.
This lets us see which nutrients really supply mitochondrial metabolites, not just which pathways are “upregulated.”
2/ Textbook view: many aggressive cancers “burn fat” (fatty acid oxidation, FAO) as a major mitochondrial fuel for ATP production.
We asked a basic question: when FAO capacity is high, how much does fat actually contribute to mitochondrial metabolism compared with other fuels?
1/ Updated preprint (v2) out on bioRxiv! A wonderful team effort with @nancyts.bsky.social, Lake-Ee Quek and others.
“Capacity-Contribution Paradox: Fatty Acid Oxidation Compensates for Low Glucose-Derived Acetyl-CoA in Cancer”
Link:
www.biorxiv.org/content/10.1...
Australian #NHMRC Ideas grants are out. 8.1% success rate. Lowest since the scheme began. Congrats to the successful few, as it looks like less than 200 were funded. 🧪
It's that but it is also what behaviours are required to survive. The concentration of particular attributes is a likely driver of the current poor status of Uni's.
Mitochondria-organelle crosstalk in establishing compartmentalized metabolic homeostasis
www.cell.com/molecular-ce...
8% success rate...
Measuring mitochondrial membrane potential
@marcliesa.bsky.social , Guillermo Martínez-Corrales et al @ibmb-csic.bsky.social comment on common misinterpretation of mitochondrial membrane potential measurements & suggest guidelines for accurate determination in cells
www.embopress.org/doi/full/10....
As a reviewer, please don't overuse AI to write your grants. I understand the need for a quick editing/grammar check, but the structure of the paragraphs and the logic is absolutely awful. I can spot it in a nanosecond.
Excited to share our study out in @natcellbio.nature.com! Led by @mikelangelipid.bsky.social, we identify the first #LipidDroplet lipid quality control pathway: LD-localized FSP1 protects stored lipids from oxidative damage and prevents LD-initiated #ferroptosis.
www.nature.com/articles/s41...
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
Not really. We went in with an open mind and not constrained by a belief that genetics explains all in cancer biology. We are physiologists after all.
reactant and product metabolite ratios revealed metabolic pathways differences between cancer subtypes and noncancer cell lines by @hoylipidlab.bsky.social @sydneyprecisionds.bsky.social @nancyts.bsky.social ➡️ www.embopress.org/doi/full/10....
This is such an incredible paper. Must read if you care about metabolites and cores organ interactions. For me most interesting finding is that the liver is NOT the only organ that converts cholesterol to bile acids. But ther are so many cool onserbwtions www.cell.com/cell/abstrac...
Can we use what we’ve learned so far about #immunometabolism in macrophages and neutrophils as cancer immunotherapy? Not yet, but someday. I’m happy to share our latest review, summarizing the state of the field in the context of #myeloidcells and #lungcancer
www.sciencedirect.com/science/arti...
Many thanks to the very helpful reviewers and editor, and the support from @sydney.edu.au Robinson Fellowship, @sydneyprecisionds.bsky.social , @sydney-crf.bsky.social SoMS and Charles Perkins Centre
Ultimately, we believe that there is significant potential of pathway-centric approaches to reveal new aspects of cellular metabolism from metabolomic data.
Finally, In silico analyses of loss-of-function and drug sensitivity screens showed that Cluster 4 cells were more susceptible to gene deletion and drug targeting of glutamine metabolism and OXPHOS than cells in Cluster 3.
Notably, Cluster 4 cells had high TCA cycle metabolites / pyruvate ratios, produced more lactate yet consumed less glucose and glutamine, and greater OXPHOS activity compared to Cluster 3 cells with low TCA cycle metabolite ratios; explained by more glutamine cataplerotic efflux and not glycolysis.
Our starting point was to determine if cancer cells can be clustered into subtypes based on metabolic pathway activity. By calculating pathway-centric metabolite ratios, we identified 5 clusters that were not explained by media composition, tissue type or origin, or mutational status.
Incredibly proud of our latest publication in @molsystbiol.org led by @nancyts.bsky.social in collab w/ Jean Yang and Lake-Ee Quek - www.embopress.org/doi/full/10....
We curated targeted metabolomic data into pathway-centric ratios and identified subclusters of cancer cells with distinct features.
Our group leader Prof Nigel Turner was interviewed for the Guardian earlier this week, discussing the hype and hope for NAD+ boosters as anti-ageing therapeutics. Read what he (and our collaborator A/Prof Lindsay Wu) had to say about it here: www.theguardian.com/australia-ne... 🧪
A Future Made in Australia … as long as no new knowledge is needed.
