The role of nitric oxide signalling in yeast stress response and cell death.

Abstract

Abstract Nitric oxide (NO) is a small gaseous molecule and free radical with important and distinct roles in diverse physiological functions in biological systems. The relevance of NO as a signalling molecule is well known, particularly in neurons as a neurotransmitter, in blood vessels as a regulator of aggregation and in cells of the immune system, where it participates in the host response to invading pathogenic microbes. NO is synthesized by the conversion of L-arginine to L-citrulline, a reaction that is catalysed by nitric oxide synthase (NOS). Once generated, NO may rapidly react with superoxide anions forming peroxynitrite (OONO-); both molecules are reactive nitrogen species (RNS). NO can also react in a slower rate with O2 and with metal ions such as iron and copper. Reactive oxygen species (ROS) play a major role in NO signalling and can affect NO availability from its production to post-production scavenging. Moreover, ROS/RNS are able to promote specific post-translational modifications, including S-nitrosation and tyrosine nitration, which both have an impact on protein function. The synthesis of NO and orthologues of mammalian NOS enzymes have been described in eukaryotes, including birds, fish and amphibians, and in prokaryotes. However, plants and the higher fungal species - representatives of the ascomycetes and zygomycetes - do not have a protein with sequence similarity to known mammalian type NOS enzymes, although they do display a NOS-like activity that indicates the presence of an enzyme(s) that is structurally unrelated to the mammalian counterparts. While the origin of NO in yeast cells is still debatable, several reports have implicated NO signalling in stress response and programmed cell death mechanisms in yeast. In this chapter, the state of the art of the biosynthesis and functions of NO in the yeast Saccharomyces cerevisiae is reviewed, with particular emphasis on stress responses and cell death.