Mitochondrial type I nitric oxide synthase physically interacts with cytochrome c oxidase

Persichini, Tiziana; Mazzone, Valeria; Polticelli, Fabio; Moreno, Sandra; Venturini, Giorgio; Clementi, Emilio; Colasanti, Marco

doi:10.1016/j.neulet.2005.04.085

Cited by 81 publications

(60 citation statements)

References 33 publications

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“…Moreover, complex I is a target for reversible inhibition by Snitrosation of critical thiol residues, because its inhibition by NO can be reversed by light or reagents containing thiol groups (14). These findings are in accordance with the structural and functional interaction observed among complexes I and IV and mtNOS (49,106). A physical proximity of mtNOS with the COOH-terminal peptide of the Va subunit of cytochrome c oxidase was shown by electron microscopic immunolocalization and coimmunoprecipitation studies.…”

Section: Role Of No In the Regulation Of Heart Functionsupporting

confidence: 78%

“…A physical proximity of mtNOS with the COOH-terminal peptide of the Va subunit of cytochrome c oxidase was shown by electron microscopic immunolocalization and coimmunoprecipitation studies. Other report showed that not only complex IV but also complex I proteins immunoprecipitate with intramitochondrial and translocated nNOS, which indicates a direct molecular interaction between mtNOS and complexes I and IV (49,106).…”

Section: Role Of No In the Regulation Of Heart Functionmentioning

confidence: 90%

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Strategic localization of heart mitochondrial NOS: a review of the evidence

Zaobornyj

Ghafourifar²

2012

American Journal of Physiology-Heart and Circulatory Physiology

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chondria play a central role in cell energy provision and in signaling. Nitric oxide (NO) is a free radical with primary regulatory functions in the heart and involved in a broad array of key processes in cardiac metabolism. Specific NO synthase (NOS) isoforms are confined to distinct locations in cardiomyocytes. The present article reviews the chemical reactions through which NO interacts with biomolecules and exerts some of its crucial roles. Specifically, the article discusses the reactions of NO with mitochondrial targets and the subcellular localization of NOS within the myocardium and analyzes the available data about heart mitochondrial NOS activity and identity. The article also describes the regulation of heart mtNOS by the distinctive mitochondrial environment by showing the effects of Ca 2ϩ , O2, L-arginine, mitochondrial transmembrane potential, and the metabolic states on heart mitochondrial NO production. The article depicts the effects of NO on heart function and highlights the relevance of NO production within mitochondria. Finally, the evidence on the functional implications of heart mitochondrial NOS is delineated with emphasis on chronic hypoxia and ischemia-reperfusion studies. mitochondrial nitric oxide synthase; calcium; transmembrane potential; hypoxia; ischemia-reperfusion SINCE THE RECOGNITION OF MITOCHONDRIA as the powerhouses of the cells, numerous studies have shown that these organelles play a central role in various biological processes. Under physiological conditions, mitochondria provide the cell with both the energy and the signals involved in the genetic expression and metabolic regulation (35). About two decades ago, the discovery that nitric oxide (NO) is the endothelium-derived relaxing factor caused a paradigm shift in the understanding of cardiovascular physiology and pathophysiology (68,102). NO is a gaseous uncharged 30-Da molecule. It is highly diffusible in aqueous and lipid phases and possesses a biochemistry that supports its role as one of the most versatile molecules in various biological regulatory and signaling processes (76,86,134).In the cardiovascular system, NO plays integral roles not only in the regulation of vascular smooth muscle tone but also in the function of ion channels, myocyte contraction, O 2 consumption, apoptosis, and hypertrophic myocardial remodeling (36, 92). In cardiac endothelial cells and myocytes, NO is generated by NO synthase (NOS) isozymes: neuronal NOS (nNOS or NOS1), inducible NOS (iNOS or NOS2), and endothelial NOS (eNOS or NOS3) (71, 75). Initially, eNOS was considered to be the only isoform constitutively expressed in myocytes and thus the source of NO involved in the autocrine regulation of myocardial contraction and Ca 2ϩ homeostasis (7, 37). However, subsequent studies showed that NOS is targeted to the cardiac sarcoplasmic reticulum (SR) (137) and localized in cardiac mitochondria (72). Additionally, iNOS has been shown to be expressed in the myocardium upon induction by cytokines (8) during inflammatory responses implicated in...

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Section: Role Of No In the Regulation Of Heart Functionsupporting

confidence: 78%

Section: Role Of No In the Regulation Of Heart Functionmentioning

confidence: 90%

Strategic localization of heart mitochondrial NOS: a review of the evidence

Zaobornyj

Ghafourifar²

2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…In addition, new isoforms or mitochondrial variants of NOS (mtNOS) have since been described in rat liver (Ghafourifar and Richter, 1997;Giulivi et al, 1998), thymus (Bustamante et al, 2000), and brain (Riobo et al, 2002). mtNOS is bound to mitochondrial cytochrome c oxidase (COX) (Persichini et al, 2005) and to complex I (Franco et al, 2006), thus favoring a steric relationship between the released NO and the control of respiration. NO is critical for numerous biological processes, including PCD, and it functions through both cGMPdependent and-independent pathways.…”

Section: No Production In Mammalian and Plant Cellsmentioning

confidence: 99%

Nitric oxide: promoter or suppressor of programmed cell death?

et al. 2010

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Nitric oxide (NO) is a short-lived gaseous free radical that predominantly functions as a messenger and effector molecule. It affects a variety of physiological processes, including programmed cell death (PCD) through cyclic guanosine monophosphate (cGMP)-dependent andindependent pathways. In this field, dominant discoveries are the diverse apoptosis networks in mammalian cells, which involve signals primarily via death receptors (extrinsic pathway) or the mitochondria (intrinsic pathway) that recruit caspases as effector molecules. In plants, PCD shares some similarities with animal cells, but NO is involved in PCD induction via interacting with pathways of phytohormones. NO has both promoting and suppressing effects on cell death, depending on a variety of factors, such as cell type, cellular redox status, and the flux and dose of local NO. In this article, we focus on how NO regulates the apoptotic signal cascade through protein S-nitrosylation and review the recent progress on mechanisms of PCD in both mammalian and plant cells.

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“…There exist three canonical isoforms [neuronal (NOS I or nNOS), inducible (NOS II), and endothelial (NOS III)] and a significant number of spliced and posttranslationally modified variants. In addition, new isoforms or mitochondrial variants of NOS (mtNOS) were recently described in rat liver (60,63), thymus (29), and brain (119); mtNOS is bound to mitochondrial PDZ domains of COX (57,103) and to complex I (57), thus favoring a steric relationship between the released NO, vectorially directed to the matrix and inner membrane, and the control of respiration. In pathological conditions such as extreme hypoxia, mitochondrial NO could come either from stimulated NOS (116,142) or from the reduction of nitrite by COX (39).…”

Section: Nitric Oxide In Mitochondriamentioning

confidence: 99%

Mitochondrial nitric oxide in the signaling of cell integrated responses

Carreras¹,

Poderoso²

2007

American Journal of Physiology-Cell Physiology

116

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Carreras MC, Poderoso JJ. Mitochondrial nitric oxide in the signaling of cell-integrated responses. Am J Physiol Cell Physiol 292: C1569 -C1580, 2007; doi:10.1152/ajpcell.00248.2006.-Mitochondria are the specialized organelles for energy metabolism, but, as a typical example of system biology, they also activate a multiplicity of pathways that modulate cell proliferation and mitochondrial biogenesis or oppositely promote cell arrest and programmed cell death by a limited number of oxidative or nitrosative reactions. These reactions are influenced by matrix nitric oxide (NO) steady-state concentration, either from local production or by gas diffusion to mitochondria from the canonical sources. Likewise, in a range of ϳ30 -200 nM, NO turns mitochondrial O 2 utilization down by binding to cytochrome oxidase and elicits a burst of superoxide anion and hydrogen peroxide that diffuses outside mitochondria. Depending on NO levels and antioxidant defenses, more or less H 2O2 accumulates in cytosol and nucleus, and the resulting redox grading contributes to dual activation of proliferating and proapoptotic cascades, like ERK1/2 or p38 MAPK. Moreover, these sequential activating pathways participate in rat liver and brain development and in thyroid modulation of mitochondrial metabolism and contribute to hypothyroid phenotype through complex I nitration. On the contrary, lack of NO disrupts pathways like S-nitrosylation or H 2O2 production and likewise is a gateway to disease in amyotrophic lateral sclerosis with superoxide dismutase 1 mutations or to cancer proliferation.peroxynitrite; hydrogen peroxide; mitochondrial nitric oxide synthase; mitogenactivated protein kinase MITOCHONDRIA PLAY A PIVOTAL role in cell physiology, producing the cellular energy and acting as signaling organelles. A mitochondria-based network elicits a multiplicity of effects and responses, depending on the course of cell life and on the environmental stimuli. This organization resulted from the selective pressure applied on eukaryotes to evolve the original endosymbiont process between bacteria, i.e., Cyanobacteria sp., and the primordial prokaryote structure. Accordingly, contribution of mitochondria includes several cohorts of integrated biochemical pathways shared with nucleus and mainly directed to execute the different cell programs or with the plasma membrane to elicit the responses to environmental challenges. Interestingly, mitochondrial pathways involve a limited number of reactions; depending on the steady-state concentrations of substrates and products and on the rate of oxidative reactions, there exist dual or even opposite effects on cell responses. NITRIC OXIDE IN MITOCHONDRIAMitochondria are the central organelles in cell bioenergetics. Most available oxygen is consumed in the electron transfer chain, placed in the inner membrane of the two membranes that limit the differentiated mitochondrial compartment. Electron transfer through mitochondrial complexes I, III, and IV is joined to proton pumping across the inner membrane, creat...

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Mitochondrial type I nitric oxide synthase physically interacts with cytochrome c oxidase

Cited by 81 publications

References 33 publications

Strategic localization of heart mitochondrial NOS: a review of the evidence

Strategic localization of heart mitochondrial NOS: a review of the evidence

Nitric oxide: promoter or suppressor of programmed cell death?

Mitochondrial nitric oxide in the signaling of cell integrated responses

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