Eukaryotic cells evolved a very sophisticated system to sense low cellular ATP levels via the serine/threonine kinase AMP-activated protein kinase (AMPK). Under conditions of low energy, AMPK phosphorylates specific enzymes and growth control nodes to increase ATP generation and decrease ATP consumption. In the past decade, the discovery of numerous new AMPK substrates has led to a more complete understanding of the minimal number of steps required to re-program cellular metabolism from anabolism to catabolism. This energy switch suppresses pro-growth pathways (mTORC1 and fatty acid synthesis) while inducing autophagy and lysosomal function. Recent studies have revealed that one ancestral function of AMPK is to promote mitochondrial health, via stimulation of autophagy, mitochondrial fission, and mitochondrial biogenesis. Here will present new data from our lab identifying key new steps and players in the mechanisms of AMPK controls mitochondrial homeostasis.