Autophagy and ammonia.

Autophagy plays an important role in the cellular response to a variety of metabolic stress conditions thus contributing to the maintenance of intracellular homeostasis. Studies in yeast have defined the genetic components involved in the initiation of autophagy as well as the progression through the autophagic cascade. The yeast kinase Atg1 initiates autophagy in response to nutrient limitation in a TOR-dependent manner. The ulk family of genes encodes the mammalian orthologue of yeast Atg1. Our recent work using mouse embryonic fibroblast (MEF) cell lines deficient for both ulk1 and ulk2, has revealed that autophagy induction is more complex in mammals than in yeast. Furthermore, these data confirm the surprising finding that a by-product of amino acid metabolism, ammonia, is a strong inducer of autophagy, as first shown by the Abraham laboratory.