A cellular energy sensor activated when ATP levels are low (e.g., during exercise or fasting). AMPK activation promotes glucose uptake, fatty acid oxidation, mitochondrial biogenesis, and autophagy. AICAR (a nucleoside analog, not a peptide) activates AMPK indirectly via its intracellular metabolite ZMP; the mitochondrial-derived peptide MOTS-c also activates AMPK signaling.