The function and the role of the mitochondrial glycerol-3-phosphate dehydrogenase in mammalian tissues.
TL;DR: This review summarizes the present knowledge on the structure and regulation of mGPDH and discusses its metabolic functions, reactive oxygen species production and tissue and organ specific roles in mammalian mitochondria at physiological and pathological conditions.
About: This article is published in Biochimica et Biophysica Acta.The article was published on 2013-03-01 and is currently open access. It has received 300 citations till now. The article focuses on the topics: Glycerophosphate shuttle & Respiratory chain.
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TL;DR: This Review discusses how mitochondria catabolize nutrients for energy, generate biosynthetic precursors for macromolecules, compartmentalize metabolites for the maintenance of redox homeostasis and function as hubs for metabolic waste management.
Abstract: Although classically appreciated for their role as the powerhouse of the cell, the metabolic functions of mitochondria reach far beyond bioenergetics. In this Review, we discuss how mitochondria catabolize nutrients for energy, generate biosynthetic precursors for macromolecules, compartmentalize metabolites for the maintenance of redox homeostasis and function as hubs for metabolic waste management. We address the importance of these roles in both normal physiology and in disease.
786 citations
TL;DR: Comparing the genome of Tibetan wild boars with those of neighboring Chinese domestic pigs further showed the impact of thousands of years of artificial selection and different signatures of selection in wild boar and domestic pig.
Abstract: We report the sequencing at 131× coverage, de novo assembly and analyses of the genome of a female Tibetan wild boar. We also resequenced the whole genomes of 30 Tibetan wild boars from six major distributed locations and 18 geographically related pigs in China. We characterized genetic diversity, population structure and patterns of evolution. We searched for genomic regions under selection, which includes genes that are involved in hypoxia, olfaction, energy metabolism and drug response. Comparing the genome of Tibetan wild boar with those of neighboring Chinese domestic pigs further showed the impact of thousands of years of artificial selection and different signatures of selection in wild boar and domestic pig. We also report genetic adaptations in Tibetan wild boar that are associated with high altitudes and characterize the genetic basis of increased salivation in domestic pig.
412 citations
TL;DR: Recent advances in the understanding of the molecular mechanisms of NAD -regulated physiological responses to stresses, the contribution of NAD + deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention are summarized.
Abstract: Nicotinamide adenine dinucleotide (NAD+) and its metabolites function as critical regulators to maintain physiologic processes, enabling the plastic cells to adapt to environmental changes including nutrient perturbation, genotoxic factors, circadian disorder, infection, inflammation and xenobiotics. These effects are mainly achieved by the driving effect of NAD+ on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions. Besides, multiple NAD+-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA, RNA and proteins, or releasing second messenger cyclic ADP-ribose (cADPR) and NAADP+. Prolonged disequilibrium of NAD+ metabolism disturbs the physiological functions, resulting in diseases including metabolic diseases, cancer, aging and neurodegeneration disorder. In this review, we summarize recent advances in our understanding of the molecular mechanisms of NAD+-regulated physiological responses to stresses, the contribution of NAD+ deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.
282 citations
TL;DR: Recognition of live bacteria by macrophages transiently decreased assembly of the ETC complex I and CI-containing super-complexes and switched the relative contributions of CI and CII to mitochondrial respiration.
Abstract: Garaude and colleagues show that innate immunological sensing of live bacteria by macrophages elicits transient adaptations to the electron-transport chain of mitochondria.
214 citations
TL;DR: Both historical and more recent findings are discussed on the central role played by the interaction between metformin and the mitochondria in its cellular mechanism of action.
Abstract: Metformin is a drug from the biguanide family that is used for decades as the first-line therapeutic choice for the treatment of type 2 diabetes. Despite its worldwide democratization, owing to its clinical efficacy, high safety profile and cheap cost, the exact mechanism(s) of action of this anti-hyperglycemic molecule with pleiotropic properties still remains to be fully elucidated. The concept that metformin would exert some of its actions though modulation of the mitochondrial bioenergetics was initially forged in the 50s but undeniably revived at the beginning of the twenty-first century when it was shown to induce a weak but specific inhibition of the mitochondrial respiratory-chain complex 1. Furthermore, metformin has been reported to reduce generation of reactive oxygen species at the complex 1 and to prevent mitochondrial-mediated apoptosis, suggesting that it can protect against oxidative stress-induced cell death. Nevertheless, despite some recent progress and the demonstration of its key role in the inhibition of hepatic gluconeogenesis, the exact nature of the mitochondrial interaction between the drug and the complex 1 is still poorly characterized. Recent studies reported that metformin may also have anti-neoplastic properties by inhibiting cancer cell growth and proliferation, at least partly through its mitochondrial action. As such, many trials are currently conducted for exploring the repositioning of metformin as a potential drug for cancer therapy. In this mini-review, we discuss both historical and more recent findings on the central role played by the interaction between metformin and the mitochondria in its cellular mechanism of action.
177 citations
Cites background from "The function and the role of the mi..."
...mGPDH is a flavin-linked respiratorychain dehydrogenase belonging to the glycerol phosphate shuttle that couples the oxidation of glycerol-3-phosphate to dihydroxyacetone with reduction of FAD to FADH2 and the transfer of electrons to coenzyme Q of the ETC, contributing as such to the maintenance of the redox potential across the inner mitochondrial membrane (48)....
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References
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TL;DR: In this paper, a new strategy for predicting the topology of bacterial inner membrane proteins is proposed on the basis of hydrophobicity analysis, automatic generation of a set of possible topologies and ranking of these according to the positive inside rule.
1,661 citations
1,558 citations
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...Cytosolic ATP production in BAT is important despite the high rate of fatty acid oxidation as mitochondria contain only tiny amount of ATP synthase [50,51] and all energy generated by OXPHOS is released by the action of uncoupling protein (UCP1) as heat [52]....
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851 citations
"The function and the role of the mi..." refers background in this paper
...Stimulation of insulin secretion by glucose involves a rise in the cytoplasmic concentration of Ca [107] caused by the closure of ATP-sensitive K channels in the plasma membrane, membrane depolarization, and influx of Ca through voltage-sensitive channels [108,109]....
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TL;DR: In late gestation increased oxidative stress is seen in pregnancies complicated by diabetes, IUGR, and preeclampsia in association with increased trophoblast apoptosis and deportation and altered placental vascular reactivity.
Abstract: Pregnancy is a state of oxidative stress arising from increased placental mitochondrial activity and production of reactive oxygen species (ROS), mainly superoxide anion. The placenta also produces other ROS including nitric oxide, carbon monoxide, and peroxynitrite which have pronounced effects on placental function including trophoblast proliferation and differentiation and vascular reactivity. Excessive production of ROS may occur at certain windows in placental development and in pathologic pregnancies, such as those complicated by preeclampsia and/or IUGR, overpowering antioxidant defenses with deleterious outcome. In the first trimester, establishment of blood flow into the intervillous space is associated with a burst of oxidative stress. The inability to mount an effective antioxidant defense against this results in early pregnancy loss. In late gestation increased oxidative stress is seen in pregnancies complicated by diabetes, IUGR, and preeclampsia in association with increased trophoblast apoptosis and deportation and altered placental vascular reactivity. Evidence for this oxidative stress includes increased lipid peroxides and isoprostanes and decreased expression and activity of antioxidants. The interaction of nitric oxide and superoxide produces peroxynitrite, a powerful prooxidant with diverse deleterious effects including nitration of tyrosine residues on proteins thus altering function. Nitrative stress, subsequent to oxidative stress is seen in the placenta in preeclampsia and diabetes in association with altered placental function.
738 citations
"The function and the role of the mi..." refers background in this paper
...Oxidative stress in pregnancy, namely hypoxia/reoxygenation in the 1 trimester results in increased oxygen tension that leads to increased ROS production in placenta, associated with oxidative damage of proteins and increase in expression of antioxidative enzymes [128]....
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TL;DR: It is demonstrated the existence of a functional respirasome and a structural organization model is proposed that accommodates these findings.
737 citations
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...be respiratory active when using succinate as a substrate [93]....
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