Life, death, and the metabolically controlled protein acetylome

The complex signaling pathways that control cellular fate can be intimately influenced by metabolic status. Although the ability of nutrients to influence intracellular decisions has been appreciated for some time, the complex signaling mechanisms linking metabolic inputs to cell proliferation and death are not fully understood. An emerging theme in the literature is that intracellular metabolite levels can directly influence cell fate decisions through modulation of nutrient-derived protein modifications. It appears that varying the level of intracellular metabolites can alter the abundance of post-translational modifications, both by altering the availability of donor substrates and changing the activity of the nutrient-sensitive enzymes regulating these reactions. We focus here on protein acetylation, a modification that can modulate both cell proliferation and cell death in response to changes in extracellular nutrient supply.