Ammonia and autophagy: An emerging relationship with implications for disorders with hyperammonemia

Abstract (Macro)autophagy/autophagy is a highly regulated lysosomal degradative process by which cells recycle their own nutrients, such as amino acids and other metabolites, to be reused in different biosynthetic pathways. Ammonia is a diffusible compound generated daily from catabolism of nitrogen‐containing molecules and from gastrointestinal microbiome. Ammonia homeostasis is tightly controlled in humans and ammonia is efficiently converted by the healthy liver into non‐toxic urea (through ureagenesis) and glutamine (through glutamine synthetase). Impaired ammonia detoxification leads to systemic hyperammonemia, a life‐threatening condition resulting in detrimental effects on central nervous system. Here, we review current understanding on the role of ammonia in modulation of autophagy and the potential implications in the pathogenesis and treatment of disorders with hyperammonemia.