Proton-Translocating Nicotinamide Nucleotide Transhydrogenase: A Structural Perspective

Zhang, Qinghai; Padayatti, Pius S.; Leung, Josephine H.

doi:10.3389/fphys.2017.01089

Cited by 24 publications

(14 citation statements)

References 56 publications

(76 reference statements)

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“…Conversion of NAD + to NADP + is catalyzed by NAD + kinase consuming ATP molecules for needed free energy [ 30 ]. Nicotinamide nucleotide transhydrogenase (NNT) catalyzes a reversible reaction, NADH + NADP + ⇌ NAD + + NADPH [ 31 ]. NAD(H) and NADP(H) play as cofactors or coenzymes in a myriad of oxidation-reduction reactions in biological systems [ 32 ].…”

Section: Metabolism Of Nicotinamidementioning

confidence: 99%

Mechanistic Basis and Clinical Evidence for the Applications of Nicotinamide (Niacinamide) to Control Skin Aging and Pigmentation

Boo

2021

Antioxidants

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Vitamin B3 (nicotinic acid, niacin) deficiency causes the systemic disease pellagra, which leads to dermatitis, diarrhea, dementia, and possibly death depending on its severity and duration. Vitamin B3 is used in the synthesis of the NAD+ family of coenzymes, contributing to cellular energy metabolism and defense systems. Although nicotinamide (niacinamide) is primarily used as a nutritional supplement for vitamin B3, its pharmaceutical and cosmeceutical uses have been extensively explored. In this review, we discuss the biological activities and cosmeceutical properties of nicotinamide in consideration of its metabolic pathways. Supplementation of nicotinamide restores cellular NAD+ pool and mitochondrial energetics, attenuates oxidative stress and inflammatory response, enhances extracellular matrix and skin barrier, and inhibits the pigmentation process in the skin. Topical treatment of nicotinamide, alone or in combination with other active ingredients, reduces the progression of skin aging and hyperpigmentation in clinical trials. Topically applied nicotinamide is well tolerated by the skin. Currently, there is no convincing evidence that nicotinamide has specific molecular targets for controlling skin aging and pigmentation. This substance is presumed to contribute to maintaining skin homeostasis by regulating the redox status of cells along with various metabolites produced from it. Thus, it is suggested that nicotinamide will be useful as a cosmeceutical ingredient to attenuate skin aging and hyperpigmentation, especially in the elderly or patients with reduced NAD+ pool in the skin due to internal or external stressors.

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Section: Metabolism Of Nicotinamidementioning

confidence: 99%

Mechanistic Basis and Clinical Evidence for the Applications of Nicotinamide (Niacinamide) to Control Skin Aging and Pigmentation

Boo

2021

Antioxidants

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“…It has also been found that mitochondria contain a matrix-associated glucose-6-phosphate dehydrogenase (G6PDH) isozyme, which has been speculated to play a role in the production of mitochondrial ribose sugars for nucleotide biosynthesis [ 33 ]. Unlike the other NADPH producers, which simply couple the oxidation of carbon to the reduction of NADP + , NNT actually assembles in the mitochondrial inner membrane and couples proton return to the matrix to the transfer of a hydride from NADH to NADP + [ 34 ].…”

Section: Mitochondrial H 2 O 2 mentioning

confidence: 99%

Mitochondrial Antioxidants and the Maintenance of Cellular Hydrogen Peroxide Levels

Mailloux

2018

Oxidative Medicine and Cellular Longevity

159

115

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For over 40 years, mitochondrial reactive oxygen species (ROS) production and balance has been studied in the context of oxidative distress and tissue damage. However, research over the past decade has demonstrated that the mitochondria have a more complicated relationship with ROS. Superoxide (O2•−) and hydrogen peroxide (H2O2) are the proximal ROS formed by the mitochondria, and the latter molecule is used as a secondary messenger to coordinate oxidative metabolism with changes in cell physiology. Like any other secondary messenger, H2O2 levels need to be regulated through its production and degradation and the mitochondria are enriched with the antioxidant defenses required to degrade ROS formed by nutrient oxidation and respiration. Recent work has also demonstrated that these antioxidant systems also carry the capacity to clear H2O2 formed outside of mitochondria. These observations led to the development of the postulate that the mitochondria serve as “ROS stabilizing devices” that buffer cellular H2O2 levels. Here, I provide an updated view on mitochondrial ROS homeostasis and discuss the “ROS stabilizing” function of the mitochondria in mammalian cells. This will be followed by a hypothetical discussion on the potential function of the mitochondria and proton motive force in degrading cellular H2O2 signals emanating from cytosolic enzymes.

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“…A TMHMM search [19] suggested that EgNNT1 contained at least 12 transmembrane domains. According to the localization of NNTs in other organisms [20], EgNNT1 was predicted to localize in the mitochondrial inner membrane.…”

Section: Effect Of Egnnt1 Silencing In the Aerobic And Anaerobic Culturesmentioning

confidence: 99%

NADPH‐to‐NADH conversion by mitochondrial transhydrogenase is indispensable for sustaining anaerobic metabolism in Euglena gracilis

et al. 2021

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after first online publication: the abbreviations have been updated for clarity] Edited by Peter BrzezinskiEuglena gracilis produces ATP in the anaerobic mitochondria with concomitant wax ester formation, and NADH is essential for ATP formation and fatty acid synthesis in the mitochondria. This study demonstrated that mitochondrial cofactor conversion by nicotinamide nucleotide transhydrogenase (NNT), converting NADPH/NAD + to NADP + /NADH, is indispensable for sustaining anaerobic metabolism. Silencing of NNT genes significantly decreased wax ester production and cellular viability during anaerobiosis but had no such marked effects under aerobic conditions. An analogous phenotype was observed in the silencing of the gene encoding a mitochondrial NADP + -dependent malic enzyme. These results suggest that the reducing equivalents produced in glycolysis are shuttled to the mitochondria as malate, where cytosolic NAD + regeneration is coupled with mitochondrial NADPH generation.

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Proton-Translocating Nicotinamide Nucleotide Transhydrogenase: A Structural Perspective

Cited by 24 publications

References 56 publications

Mechanistic Basis and Clinical Evidence for the Applications of Nicotinamide (Niacinamide) to Control Skin Aging and Pigmentation

Mechanistic Basis and Clinical Evidence for the Applications of Nicotinamide (Niacinamide) to Control Skin Aging and Pigmentation

Mitochondrial Antioxidants and the Maintenance of Cellular Hydrogen Peroxide Levels

NADPH‐to‐NADH conversion by mitochondrial transhydrogenase is indispensable for sustaining anaerobic metabolism in Euglena gracilis

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