%0 Journal Article
%T Established Principles and Emerging Concepts on the Interplay between Mitochondrial Physiology and S-(De)nitrosylation: Implications in Cancer and Neurodegeneration
%A Giuseppina Di Giacomo
%A Salvatore Rizza
%A Costanza Montagna
%A Giuseppe Filomeni
%J International Journal of Cell Biology
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/361872
%X S-nitrosylation is a posttranslational modification of cysteine residues that has been frequently indicated as potential molecular mechanism governing cell response upon redox unbalance downstream of nitric oxide (over)production. In the last years, increased levels of S-nitrosothiols (SNOs) have been tightly associated with the onset of nitroxidative stress-based pathologies (e.g., cancer and neurodegeneration), conditions in which alterations of mitochondrial homeostasis and activation of cellular processes dependent on it have been reported as well. In this paper we aim at summarizing the current knowledge of mitochondria-related proteins undergoing S-nitrosylation and how this redox modification might impact on mitochondrial functions, whose impairment has been correlated to tumorigenesis and neuronal cell death. In particular, emphasis will be given to the possible, but still neglected implication of denitrosylation reactions in the modulation of mitochondrial SNOs and how they can affect mitochondrion-related cellular process, such as oxidative phosphorylation, mitochondrial dynamics, and mitophagy. 1. Introduction Nitric oxide (NO) is a gaseous and membrane diffusible radical molecule generated by the NADPH-dependent enzyme NO synthase (NOS) from L-arginine and oxygen [1, 2]. Three are the major isoforms of NOS that have been so far identified, namely, neuronal and endothelial NOS (nNOS or NOS1 and eNOS or NOS3, resp.), which are constitutively active, and the cytokine-inducible NOS (iNOS or NOS2), mainly expressed in immune system to face host attack [3, 4]. The biochemical characterization of NO as new signaling molecule, as well as its implication in cardiovascular function earned Furchgott, Ignarro, and Murad the Nobel prize in Physiology or Medicine in 1998. In particular, they provided the most consistent lines of evidence that NO activates guanylyl cyclase by a direct binding to heme iron (Fe-nitrosylation) and induces cGMP-mediated signaling [5], thus regulating blood vessel tone [6], immune response [7], neurotransmission [8], and many other organic functions. NO can also react with other oxygen-derived radical and nonradical species (ROS), thus generating more dangerous reactive nitrogen species (RNS, e.g., peroxynitrite, ONOO£¿), which target proteins and irreversibly affect their structure and function, a phenomenon commonly known as nitrosative (or nitroxidative) stress [9]. Tyrosine nitration is one of the modifications occurring under conditions of NO overproduction and mostly depends on the reaction with ONOO£¿ [10]. It consists of
%U http://www.hindawi.com/journals/ijcb/2012/361872/