Glutaminase: A multifaceted protein not only involved in generating glutamate

The protein glutaminase has been traditionally considered as a mitochondrial enzyme, playing a key role in the energy and nitrogen metabolism of mammalian cells. However, new experimental evidence in the last few years has challenged this simplified view. The recent discovery of novel extramitochondrial localizations, the identification of potential protein interacting partners, the existence of multiple transcripts for mammalian glutaminase genes, and the presence of signature sequences and protein motifs on its sequence support the notion of glutaminase being a multifaceted protein, which may be involved in other functions besides glutamate generation from glutamine. In this short review, we will briefly summarize recent works on glutaminase proteins in mammals, with particular emphasis in brain studies. This experimental evidence will then be used to highlight new potential roles for this classical metabolic enzyme.