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

We welcome all feedback and hope you enjoy the paper! /end

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/

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/

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/

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/

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/

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/