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The ability of NAD(+) to act as a metabolic cofactor and as a rate-limiting cosubstrate for many enzymes, particularly the sirtuins, has led to the identification of a pivotal role of NAD(+) levels in the control of whole-body metabolic homeostasis. Bioavailability and compartmentalization of NAD(+) have become highly relevant issues that we need to understand in order to elucidate how NAD(+) acts both as a readout of the metabolic milieu and as an effector triggering appropriate cellular adaptations.
Cantó et al. (Sat,) studied this question.
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