I'm excited to share our latest story from the @lydiafinley.bsky.social lab, where we show that it's not just whether cells take up nutrients that matters, but how and where those metabolites are used. Out now in @naturemetabolism.bsky.social: rdcu.be/ejFTs 1/ - ThreadSky

I'm excited to share our latest story from the
@lydiafinley.bsky.social lab, where we show that it's not just whether cells take up nutrients that matters, but how and where those metabolites are used. Out now in @naturemetabolism.bsky.social: https://rdcu.be/ejFTs 1/

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btjackson.bsky.social•34 days ago

Across mammalian cell metabolism, pyruvate entry into the TCA cycle is a tightly regulated metabolic node. While TCA cycle oxidation is critical for cellular anabolism, it has important metabolic costs, specifically for cytosolic redox balance. 2/

btjackson.bsky.social•34 days ago

Any pyruvate that is captured in the mitochondria comes at the expense of NAD+ regeneration in the cytosol by LDH; moreover, the conversion of glucose to pyruvate itself requires NAD+. How do cells that burn glucose-derived pyruvate efficiently regenerate their cytosolic NAD+? 3/

btjackson.bsky.social•34 days ago

Using embryonic stem cells (ESCs) as a model where cell state is intertwined with TCA cycle dynamics, we show that avid pyruvate uptake from the extracellular environment by naive ESCs is required for NAD+ regeneration in the setting of mitochondrial pyruvate oxidation. 4/

btjackson.bsky.social•34 days ago

Pyruvate uptake by naive ESCs requires but is not limited by transporter (MCT1) levels. Rather, mitochondrial pyruvate oxidation creates a metabolic gradient that dictates the strength and direction of pyruvate transport. These are some of my favorite experiments in the paper! 5/

btjackson.bsky.social•34 days ago

In ESCs, we think pyruvate uptake is especially important in the uterine environment, which has a different nutrient composition (low glucose, high lactate) than plasma or tissue culture media. For more on how NAD+ regeneration is coordinated in other cell types, stay tuned! 6/

btjackson.bsky.social•34 days ago

Many other nuggets in the paper that couldn't have been done without my brilliant co-author Angela, the support of @lydiafinley.bsky.social and the lab (@juliabrunner.bsky.social, @katrinaparas.bsky.social and more) and a superb editorial process @naturemetabolism.bsky.social. 7/

muirlab.bsky.social•34 days ago

Super exciting work! Congratulations!

btjackson.bsky.social•34 days ago

Thank you so much for the kind words and all your excellent feedback!

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