Nitric oxide, complex I, and the modulation of mitochondrial reactive species in biology and disease

Carreras, Marı́a Cecilia; Franco, María Clara; Peralta, Jorge G.; Poderoso, Juan José

doi:10.1016/j.mam.2004.02.014

Cited by 151 publications

(103 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Treatment with the combination of mitochondrial nutrients, more significantly than with pioglitazone, normalised the activity of liver mitochondrial complexes in GK rats towards that in non-diabetic Wistar rats, suggesting that the mitochondrion is a possible target of these nutrients. That complexes I, III and IV all respond similarly is consistent with other characteristics they have in common: the activities of all three are inhibited by NO (34) , critical subunits of all three are encoded by mitochondrial genes (in contrast to complex II) and all three act to pump protons out of the mitochondrial matrix (in contrast to complex V). The increases in complexes II and V are consistent with a previous report by Ferreira et al (31) but the changes in complexes I and IV are different.…”

Section: Discussionsupporting

confidence: 81%

Mitochondrial dysfunction in the liver of type 2 diabetic Goto–Kakizaki rats: improvement by a combination of nutrients

et al. 2011

View full text Add to dashboard Cite

Treatment with a combination of four nutrients, i.e. R-a-lipoic acid, acetyl-L-carnitine, nicotinamide and biotin, just as with pioglitazone, significantly improves glucose tolerance, insulin release, plasma NEFA, skeletal muscle mitochondrial biogenesis and oxidative stress in Goto -Kakizaki (GK) rats. However, it is not known whether treatment with these nutrients can improve mitochondrial function and reduce oxidative stress in GK rats. The effects of a combination of these four nutrients on mitochondrial function, oxidative stress and apoptosis in GK rat liver were investigated. Livers of untreated GK rats showed (1) abnormal changes in the activities of mitochondrial complexes (decreases in I, III and IV and increases in II and V), (2) increases in protein oxidation, (3) decreases in antioxidant enzymes (superoxide dismutase, glutathione S-transferase, NADH-quinone oxidoreductase-1), (4) a decrease in total antioxidant capacity but increases in reduced glutathione level and glyceraldehyde 3-phosphate dehydrogenase expression and (5) significant increases in apoptosis biomarkers, including expression of p21 and p53. A 3-month treatment with the four nutrients significantly improved most of these abnormalities in GK rats, and the effects of the nutrient combination were greater than those of pioglitazone for most of these indices. These results suggest that dietary supplementation with nutrients that are thought to influence mitochondrial function may be an effective strategy for improving liver dysfunction in GK diabetic rats.Key words: R-a-Lipoic acid: Acetyl-L-carnitine: Nicotinamide: Biotin: Oxidative damage: Phase II enzymes: Apoptosis Type 2 (non-insulin-dependent) diabetes mellitus is one of the most common metabolic diseases in humans, affecting about 3 % of the human population. Clinically, it is rather a group of related diseases, characterised by chronic hyperglycaemic levels, due to an impairment in the balance among the three processes of b-cell secretion of insulin, peripheral resistance to insulin and hepatic glucose production (1,2) . Depending on several factors, such as obesity, age of onset, mode of inheritance and severity of glucose intolerance, clinical features of individuals suffering from type 2 diabetes are highly variable.Despite being one of the most common non-communicable diseases in the world, the exact mechanism (or mechanisms) leading to glucose intolerance is still not clear (1,3) . Recently, mitochondrial dysfunction due to oxidative damage has become known as a major contributor to ageing, to degenerative diseases such as cancer, and to the metabolic syndrome, obesity and type 2 diabetes (4,5) . A group of antioxidants/ metabolites which can act to improve mitochondrial function and protect mitochondria from oxidative damage, when supplemented in the diet, have been defined as mitochondrial † These authors contributed equally to this work.

show abstract

Section: Discussionsupporting

confidence: 81%

Mitochondrial dysfunction in the liver of type 2 diabetic Goto–Kakizaki rats: improvement by a combination of nutrients

et al. 2011

View full text Add to dashboard Cite

show abstract

“…This special characteristic is frequently referred as complex I syndrome, with the symptoms of reduced mitochondrial respiration with malate-glutamate and ADP and of reduced complex I activity. This complex I syndrome has been observed in aging (Navarro et al, 2005;Navarro  Boveris, 2004, in ischemia-reperfusion (Gonzalez-Flecha et al, 1993), in Parkinson's disease, and in other neurodegenerative diseases (Schapira et al, 1990a(Schapira et al, , 1990bSayre et al, 1999;Carreras et al, 2004;Schapira, 2008;, and in this study, with the addition of the increased rates of production of O2 .-and H2O2 by complex I mediated reactions, reactions with the free radicals intermediates of the lipid peroxidation process (mainly ROO·), and amine-aldehyde adduction reactions. It is now understood that the three processes above mentioned alter the native non-covalent polypeptide interactions of complex I and promote synergistically protein damage and inactivation by shifting the noncovalent bonding to covalent cross linking (Navarro et al, 2005).…”

Section: Mitochondriamentioning

confidence: 99%

Lipid Peroxidation: Chemical Mechanism, Biological Implications and Analytical Determination

Repetto¹,

Semprine²,

Boveris³

2012

Lipid Peroxidation

235

211

View full text Add to dashboard Cite

“…Therefore, the inhibition of GDC activity after GSNO treatment could have been an indirect effect of ROS induced by inhibition of complex I. It is well known that the activity of complex I of the mitochondrial electron transport chain is inhibited by nitrosothiols and peroxinitrite (Carreras et al, 2004;Dahm et al, 2006). This inhibition results in increased production of ROS, which can cause oxidative damage of GDC (Taylor et al, 2002).…”

Section: Inhibition Of Gly Decarboxylase Activity By Gsnomentioning

confidence: 99%

Regulation of Plant Glycine Decarboxylase byS-Nitrosylation and Glutathionylation

et al. 2010

View full text Add to dashboard Cite

Mitochondria play an essential role in nitric oxide (NO) signal transduction in plants. Using the biotin-switch method in conjunction with nano-liquid chromatography and mass spectrometry, we identified 11 candidate proteins that were S-nitrosylated and/or glutathionylated in mitochondria of Arabidopsis (Arabidopsis thaliana) leaves. These included glycine decarboxylase complex (GDC), a key enzyme of the photorespiratory C 2 cycle in C3 plants. GDC activity was inhibited by S-nitrosoglutathione due to S-nitrosylation/S-glutathionylation of several cysteine residues. Gas-exchange measurements demonstrated that the bacterial elicitor harpin, a strong inducer of reactive oxygen species and NO, inhibits GDC activity. Furthermore, an inhibitor of GDC, aminoacetonitrile, was able to mimic mitochondrial depolarization, hydrogen peroxide production, and cell death in response to stress or harpin treatment of cultured Arabidopsis cells. These findings indicate that the mitochondrial photorespiratory system is involved in the regulation of NO signal transduction in Arabidopsis.

show abstract

Nitric oxide, complex I, and the modulation of mitochondrial reactive species in biology and disease

Cited by 151 publications

References 54 publications

Mitochondrial dysfunction in the liver of type 2 diabetic Goto–Kakizaki rats: improvement by a combination of nutrients

Mitochondrial dysfunction in the liver of type 2 diabetic Goto–Kakizaki rats: improvement by a combination of nutrients

Lipid Peroxidation: Chemical Mechanism, Biological Implications and Analytical Determination

Regulation of Plant Glycine Decarboxylase byS-Nitrosylation and Glutathionylation

Contact Info

Product

Resources

About