De novo NAD(+) synthesis enhances mitochondrial function and improves health

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Differential role of nicotinamide adenine dinucleotide deficiency in acute and chronic kidney disease

Joseph Rutkowski, Renuga Devi Rajaram, Elena Katsyuba, Johan Auwerx, Adrienne Joëlle Laurence Mottis

Background. Nicotinamide adenine dinucleotide (NAD(+)) is a ubiquitous coenzyme involved in electron transport and a cosubstrate for sirtuin function. NAD(+) deficiency has been demonstrated in the context of acute kidney injury (AKI). Methods. We studied ...

2021

Prolyl endopeptidase-like is a (thio)esterase involved in mitochondrial respiratory chain function

Matteo Dal Peraro, Maria Josefina Marcaida Lopez

Deficiency of the serine hydrolase prolyl endopeptidase-like (PREPL) causes a recessive metabolic disorder characterized by neonatal hypotonia, feeding difficulties, and growth hormone deficiency. The pathophysiology of PREPL deficiency and the physiologic ...

CELL PRESS2021

SLC25A51 is a mammalian mitochondrial NAD(+) transporter

Kai Johnsson, Liang Wang

Mitochondria require nicotinamide adenine dinucleotide (NAD(+)) to carry out the fundamental processes that fuel respiration and mediate cellular energy transduction. Mitochondrial NAD(+) transporters have been identified in yeast and plants(1,2), but thei ...

NATURE RESEARCH2020

NAD(+) homeostasis in health and disease

Elena Katsyuba, Johan Auwerx, Mario Romani, Dina Hofer

The conceptual evolution of nicotinamide adenine dinucleotide (NAD(+)) from being seen as a simple metabolic cofactor to a pivotal cosubstrate for proteins regulating metabolism and longevity, including the sirtuin family of protein deacylases, has led to ...

2020

Brain NAD Is Associated With ATP Energy Production and Membrane Phospholipid Turnover in Humans

Rolf Gruetter, Lijing Xin, Maya Shevlyakova, Özlem Ipek

The brain requires a large amount of energy, mostly derived from the metabolism of glucose, which decreases substantially with age and neurological diseases. While mounting evidence in model organisms illustrates the central role of brain nicotinamide aden ...

FRONTIERS MEDIA SA2020

Augmented mitochondrial energy metabolism is an early response to chronic glucose stress in human pancreatic beta cells

Loïc Dayon, Isabelle Chareyron, Andreas Wiederkehr, Sofia Moco

Aims/hypothesis In islets from individuals with type 2 diabetes and in islets exposed to chronic elevated glucose, mitochondrial energy metabolism is impaired. Here, we studied early metabolic changes and mitochondrial adaptations in human beta cells durin ...

2020

Mono-, Di- and Tetra-iron Complexes with Selenium or Sulphur Functionalized Vinyliminium Ligands: Synthesis, Structural Characterization and Antiproliferative Activity

Paul Joseph Dyson, Lucinda Kate Batchelor, Silvia Schoch

A series of diiron/tetrairon compounds containing a S- or a Se-function (2a-d, 4a-d, 5a-b, 6), and the monoiron [FeCp(CO){SeC1(NMe2)(CHC3)-H-2(Me)}] (3) were prepared from the diiron mu-vinyliminium precursors [Fe2Cp2(CO)( mu-CO){mu-eta(1): eta(3)-C-3(R')( ...

2020

Pronounced α-synuclein pathology in a seeding-based mouse model is not sufficient to induce mitochondrial respiration deficits in the striatum and amygdala

Maria del Carmen Sandi Perez, Hilal Lashuel, Jean-Christophe Copin, Johannes Burtscher

Increasing evidence suggests that crosstalk between α-synuclein pathology formation and mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson’s disease and related synucleinopathies. While mitochondrial dysfunction is a well-studi ...

2020

Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans

Johan Auwerx, Richardus Houtkooper

Background: Nicotinamide riboside (NR) is an NAD(+) precursor that boosts cellular NAD(+) concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation. ...

OXFORD UNIV PRESS2020

Development of novel tools for imaging of metabolic fluxes in vivo

Tamara Maric

Bioluminescent imaging is a powerful technique that enables imaging in living organisms with high sensitivity, low background signal, low cost and without the need for radioactivity. The emitted photons are produced in the oxidation reaction of luciferin c ...

EPFL2020

Mitochondrial gene signature in the prefrontal cortex for differential susceptibility to chronic stress

Maria del Carmen Sandi Perez, Rolf Gruetter, Bart Deplancke, Antoine Timothée Cherix, Jocelin Grosse, Julie Marie Russeil, Daniel Alpern, Meltem Weger, Sriparna Ghosal

Mitochondrial dysfunction was highlighted as a crucial vulnerability factor for the development of depression. However, systemic studies assessing stress-induced changes in mitochondria-associated genes in brain regions relevant to depression symptomatolog ...

2020

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