FIGURE 2: Regulatory pathways involved in autophagy. Regulation of autoph-agy is mediated via two key conditions: starvation, determined by amino acid, glucose and lipid levels, as well as protein acetylation status. Protein acetylation is mediated via HATs, which can be inhibited by spermidine, and deacetylation is mediated via NAD⁺-dependent sirtuins. Acetyl-CoA, a product of glycolysis, is a substrate for protein acetylation. DHA is associated with low p53 levels, which translates into inactive AMPK. In absence of glucose, high AMP:ATP ratios activate AMPK, which, in further consequence, inhibits mTORC and therefore induces autophagy. High glucose levels result in high cAMP levels and therefore active PKA, which inhibits autophagy. mTORC is activated by insulin growth factors, amino acids and glucose and, in its active state, inhibits autophagy. Unsaturated fatty acids are associated with non-canonical autophagy, whereas saturated fatty acids activate PIK3C3, that converts PI to PI3P, which is associated with autophagy. These metabolites involved in regulation of autophagy are discussed in detail in the text.