Mitochondrial compartmentalization of redox processes

Cardoso, Ariel R.; Chausse, Bruno; Cunha, Fernanda Marques da; Luévano‐Martínez, Luis Alberto; Marazzi, Thire B.M.; Pessoa, Phillipe S.; Queliconi, Bruno B.; Kowaltowski, Alicia J.

doi:10.1016/j.freeradbiomed.2012.03.008

Cited by 75 publications

(54 citation statements)

References 127 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The potential for the development of markers indicating high ROS levels in a compartment-specific manner was confirmed by the effects of antioxidants designed to selectively remove ROS from mitochondria in vivo (53). The most extensively studied mitochondrion-targeted antioxidant is mitoquinone (MitoQ); it contains an antioxidant quinone moiety that is covalently linked to a lipophilic TPP + via a 10-carbon alkyl chain.…”

Section: Compartment-specific Ros Measurementmentioning

confidence: 99%

“…However, the results of two phase II human trials (with Parkinson's disease and chronic hepatitis C patients) are less convincing (333). In this respect, it should be taken into account that presence of high quantities of TPP + -conjugated probes in the mitochondria may lead to quenching, mitochondrial uncoupling, and changes in the mitochondrial function (53,165).…”

Section: Compartment-specific Ros Measurementmentioning

confidence: 99%

“…Interestingly, the inner mitochondrial membrane appears to contain a high amount of the antioxidant vitamin E (134), whereas GSH and vitamin C are important antioxidants in the mitochondrial matrix (53). Lysosomes contain high concentrations of low-molecularweight antioxidants such as GSH and vitamin C (195).…”

Section: A Intracellular and Extracellular Localization Of Antioxidantsmentioning

confidence: 99%

See 2 more Smart Citations

Nutritional Countermeasures Targeting Reactive Oxygen Species in Cancer: From Mechanisms to Biomarkers and Clinical Evidence

Samoylenko

Hossain²,

Mennerich³

et al. 2013

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Reactive oxygen species (ROS) exert various biological effects and contribute to signaling events during physiological and pathological processes. Enhanced levels of ROS are highly associated with different tumors, a Western lifestyle, and a nutritional regime. The supplementation of food with traditional antioxidants was shown to be protective against cancer in a number of studies both in vitro and in vivo. However, recent largescale human trials in well-nourished populations did not confirm the beneficial role of antioxidants in cancer, whereas there is a well-established connection between longevity of several human populations and increased amount of antioxidants in their diets. Although our knowledge about ROS generators, ROS scavengers, and ROS signaling has improved, the knowledge about the direct link between nutrition, ROS levels, and cancer is limited. These limitations are partly due to lack of standardized reliable ROS measurement methods, easily usable biomarkers, knowledge of ROS action in cellular compartments, and individual genetic predispositions. The current review summarizes ROS formation due to nutrition with respect to macronutrients and antioxidant micronutrients in the context of cancer and discusses signaling mechanisms, used biomarkers, and its limitations along with large-scale human trials.

show abstract

Section: Compartment-specific Ros Measurementmentioning

confidence: 99%

Section: Compartment-specific Ros Measurementmentioning

confidence: 99%

Section: A Intracellular and Extracellular Localization Of Antioxidantsmentioning

confidence: 99%

See 1 more Smart Citation

Nutritional Countermeasures Targeting Reactive Oxygen Species in Cancer: From Mechanisms to Biomarkers and Clinical Evidence

Samoylenko

Hossain²,

Mennerich³

et al. 2013

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

show abstract

“…Nox family reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are the prototypical source of signaling ROS in most cells [reviewed in Refs. (12,58,96,97)], even though in quantitative terms, mitochondria can predictably surpass Noxes as ROS sources in most, although likely not in all, cell types (10,25). While in mitochondria, the modular architecture is provided by the organellar structure itself, in the case of Nox NADPH oxidases, this is achieved through a regulated set of multiple protein interactions and/or posttranslational modifications associated with Nox complex assembling and traffic to specific subcellular locations, which vary according to the type of Nox isoform [reviewed in Refs.…”

Section: Introductionmentioning

confidence: 99%

Nox NADPH Oxidases and the Endoplasmic Reticulum

Laurindo

Araujo

Abrahão

2014

Antioxidants & Redox Signaling

159

138

View full text Add to dashboard Cite

Significance: Understanding isoform-and context-specific subcellular Nox reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase compartmentalization allows relevant functional inferences. This review addresses the interplay between Nox NADPH oxidases and the endoplasmic reticulum (ER), an increasingly evident player in redox pathophysiology given its role in redox protein folding and stress responses. Recent Advances: Catalytic/regulatory transmembrane subunits are synthesized in the ER and their processing includes folding, N-glycosylation, heme insertion, p22phox heterodimerization, as shown for phagocyte Nox2. Dual oxidase (Duox) maturation also involves the regulation by ER-resident Duoxa2. The ER is the activation site for some isoforms, typically Nox4, but potentially other isoforms. Such location influences redox/Nox-mediated calcium signaling regulation via ER targets, such as sarcoendoplasmic reticulum calcium ATPase (SERCA). Growing evidence suggests that Noxes are integral signaling elements of the unfolded protein response during ER stress, with Nox4 playing a dual prosurvival/proapoptotic role in this setting, whereas Nox2 enhances proapoptotic signaling. ER chaperones such as protein disulfide isomerase (PDI) closely interact with Noxes. PDI supports growth factor-dependent Nox1 activation and mRNA expression, as well as migration in smooth muscle cells, and PDI overexpression induces acute spontaneous Nox activation. Critical Issues: Mechanisms of PDI effects include possible support of complex formation and RhoGTPase activation. In phagocytes, PDI supports phagocytosis, Nox activation, and redox-dependent interactions with p47phox. Together, the results implicate PDI as possible Nox organizer. Future Directions: We propose that convergence between Noxes and ER may have evolutive roots given ER-related functional contexts, which paved Nox evolution, namely calcium signaling and pathogen killing. Overall, the interplay between Noxes and the ER may provide relevant insights in Nox-related (patho)physiology. Antioxid. Redox Signal. 20, 2755Signal. 20, -2775

show abstract

“…Indeed, when breakdown of nutrient oxidation exceeds the capacity of the ETC to assimilate the resulting electrons, mt ROS production increases (Wellen and Thompson, 2010). Furthermore during nutrient overflow, mt ROS levels are also amplified by pyruvate dehydrogenase, α-ketoglutarate 13 dehydrogenase (Cardoso et al, 2012;Starkov et al, 2004) and branched-chain ketoacids dehydrogenase activity (Tretter and Adam-Vizi, 2004). mt ROS during nutrient excess, however, are not only by-products of metabolic flux through mitochondria but can also be produced by other specific enzymatic activity, such as that of p66Shc (Trinei et al, 2013), whose activation is generally related to a nutrient overload (Pani, 2010).…”

Section: Mt Ros Threshold: From Damaging Agents To Signalling Mediatorsmentioning

confidence: 99%