Receptor

Autophagy

AMP-activated protein kinase

AMPK

Biology

Kinase

Apoptosis

Nutrient sensing

Chemistry

Energy homeostasis

Mitophagy

Metabolism

Signal transduction

Mitochondrion

Cell biology

Protein kinase A

Biochemistry

ULK1

Catabolism

Nature Reviews Molecular Cell Biology

AMP-activated protein kinase (AMPK) senses cellular energy levels and phosphorylates a variety of cellular substrates to inhibit or stimulate anabolic and catabolic processes, adjusting metabolism to energy needs. Recent studies have uncovered a crucial role of AMPK in the regulation of mitochondrial dynamics and mitophagy, further expanding its role in the control of cellular metabolism. Cells constantly adapt their metabolism to meet their energy needs and respond to nutrient availability. Eukaryotes have evolved a very sophisticated system to sense low cellular ATP levels via the serine/threonine kinase AMP-activated protein kinase (AMPK) complex. 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 reprogramme cellular metabolism from anabolism to catabolism. This energy switch controls cell growth and several other cellular processes, including lipid and glucose metabolism and autophagy. Recent studies have revealed that one ancestral function of AMPK is to promote mitochondrial health, and multiple newly discovered targets of AMPK are involved in various aspects of mitochondrial homeostasis, including mitophagy. This Review discusses how AMPK functions as a central mediator of the cellular response to energetic stress and mitochondrial insults and coordinates multiple features of autophagy and mitochondrial biology.

AMPK: guardian of metabolism and mitochondrial homeostasis