SustainedO-GlcNAcylation reprograms mitochondrial function to regulate energy metabolism

Introduction: Schisandrin which is derived from Schisandra chinensis has shown multiple pharmacological effects on various diseases including Alzheimer’s disease (AD). It is demonstrated that mitochondrial dysfunction plays an essential role in the pathogenesis of neurodegenerative disorders. Objective: Our study aims to investigate the effects of schisandrin on mitochondrial functions and metabolisms in primary hippocampal neurons. Methods: In our study, rat primary hippocampal neurons were isolated and treated with indicated dose of amyloid β1–42 (Aβ1–42) oligomer to establish a cell model of AD in vitro. Schisandrin (2 μg/mL) was further subjected to test its effects on mitochondrial function, energy metabolism, mitochondrial biogenesis, and dynamics in the Aβ1–42 oligomer-treated neurons. Results and Conclusions: Our findings indicated that schisandrin significantly alleviated the Aβ1–42 oligomer-induced loss of mitochondrial membrane potential and impaired cytochrome c oxidase activity. Additionally, the opening of mitochondrial permeability transition pore and release of cytochrome c were highly restricted with schisandrin treatment. Alterations in cell viability, ATP production, citrate synthase activity, and the expressions of glycolysis-related enzymes demonstrated the relief of defective energy metabolism in Aβ-treated neurons after the treatment of schisandrin. For mitochondrial biogenesis, elevated expression of peroxisome proliferator-activated receptor γ coactivator along with promoted mitochondrial mass was found in schisandrin-treated cells. The imbalance in the cycle of fusion and fission was also remarkably restored by schisandrin. In summary, this study provides novel mechanisms for the protective effect of schisandrin on mitochondria-related functions.

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PGC-1β: A Regulator of Mitochondrial Function with Subtle Roles in Energy Metabolism

PLoS Biology ◽

10.1371/journal.pbio.0040402 ◽

2006 ◽

Vol 4 (11) ◽

pp. e402

Author(s):

Françoise Chanut

Keyword(s):

Energy Metabolism ◽

Mitochondrial Function

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MDM2 ubiquitin-ligase down-regulate energy metabolism of cancer cells

Biopolymers and Cell ◽

10.7124/bc.0009f9 ◽

2019 ◽

Vol 35 (3) ◽

pp. 233-233

Author(s):

O. Shuvalov ◽

A. Petukhov ◽

O. Fedorova ◽

A. Daks ◽

E. Baidyuk ◽

...

Keyword(s):

Energy Metabolism ◽

Cancer Cells ◽

Ubiquitin Ligase ◽

Regulate Energy Metabolism

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Mitochondrial function and energy metabolism in cancer cells: Past overview and future perspectives

Mitochondrion ◽

10.1016/j.mito.2009.01.009 ◽

2009 ◽

Vol 9 (3) ◽

pp. 165-179 ◽

Cited By ~ 57

Author(s):

Avraham Mayevsky

Keyword(s):

Energy Metabolism ◽

Cancer Cells ◽

Mitochondrial Function ◽

Future Perspectives

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

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa072 ◽

2020 ◽

Vol 112 (2) ◽

pp. 413-426 ◽

Cited By ~ 7

Author(s):

Carlijn M E Remie ◽

Kay H M Roumans ◽

Michiel P B Moonen ◽

Niels J Connell ◽

Bas Havekes ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Composition ◽

Insulin Sensitivity ◽

Energy Metabolism ◽

Mitochondrial Function ◽

Dry Weight ◽

Metabolic Health ◽

Men And Women ◽

Nicotinamide Riboside ◽

Wet Weight

ABSTRACT Background Nicotinamide riboside (NR) is an NAD+ precursor that boosts cellular NAD+ concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation. Objectives We aimed to investigate the effects of 6 wk NR supplementation on insulin sensitivity, mitochondrial function, and other metabolic health parameters in overweight and obese volunteers. Methods A randomized, double-blinded, placebo-controlled, crossover intervention study was conducted in 13 healthy overweight or obese men and women. Participants received 6 wk NR (1000 mg/d) and placebo supplementation, followed by broad metabolic phenotyping, including hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy, muscle biopsies, and assessment of ex vivo mitochondrial function and in vivo energy metabolism. Results Markers of increased NAD+ synthesis—nicotinic acid adenine dinucleotide and methyl nicotinamide—were elevated in skeletal muscle after NR compared with placebo. NR increased body fat-free mass (62.65% ± 2.49% compared with 61.32% ± 2.58% in NR and placebo, respectively; change: 1.34% ± 0.50%, P = 0.02) and increased sleeping metabolic rate. Interestingly, acetylcarnitine concentrations in skeletal muscle were increased upon NR (4558 ± 749 compared with 3025 ± 316 pmol/mg dry weight in NR and placebo, respectively; change: 1533 ± 683 pmol/mg dry weight, P = 0.04) and the capacity to form acetylcarnitine upon exercise was higher in NR than in placebo (2.99 ± 0.30 compared with 2.40 ± 0.33 mmol/kg wet weight; change: 0.53 ± 0.21 mmol/kg wet weight, P = 0.01). However, no effects of NR were found on insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma markers of inflammation, or energy metabolism. Conclusions NR supplementation of 1000 mg/d for 6 wk in healthy overweight or obese men and women increased skeletal muscle NAD+ metabolites, affected skeletal muscle acetylcarnitine metabolism, and induced minor changes in body composition and sleeping metabolic rate. However, no other metabolic health effects were observed. This trial was registered at clinicaltrials.gov as NCT02835664

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CoenzymeQ10-Induced Activation of AMPK-YAP-OPA1 Pathway Alleviates Atherosclerosis by Improving Mitochondrial Function, Inhibiting Oxidative Stress and Promoting Energy Metabolism

Frontiers in Pharmacology ◽

10.3389/fphar.2020.01034 ◽

2020 ◽

Vol 11 ◽

Cited By ~ 2

Author(s):

Tianqi Xie ◽

Changyuan Wang ◽

Yue Jin ◽

Qiang Meng ◽

Qi Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Energy Metabolism ◽

Mitochondrial Function

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Medium-chain TAG improve energy metabolism and mitochondrial biogenesis in the liver of intra-uterine growth-retarded and normal-birth-weight weanling piglets

British Journal Of Nutrition ◽

10.1017/s0007114516000404 ◽

2016 ◽

Vol 115 (9) ◽

pp. 1521-1530 ◽

Cited By ~ 18

Author(s):

Hao Zhang ◽

Yue Li ◽

Xiang Hou ◽

Lili Zhang ◽

Tian Wang

Keyword(s):

Birth Weight ◽

Energy Metabolism ◽

Mitochondrial Biogenesis ◽

Mitochondrial Function ◽

Normal Birth Weight ◽

Gene Expressions ◽

Medium Chain ◽

Normal Birth ◽

Uterine Growth ◽

Weanling Piglets

AbstractWe previously reported that medium-chain TAG (MCT) could alleviate hepatic oxidative damage in weanling piglets with intra-uterine growth retardation (IUGR). There is a relationship between oxidative status and energy metabolism, a process involved in substrate availability and glucose flux. Therefore, the aim of this study was to investigate the effects of IUGR and MCT on hepatic energy metabolism and mitochondrial function in weanling piglets. Twenty-four IUGR piglets and twenty-four normal-birth-weight (NBW) piglets were fed a diet of either soyabean oil (SO) or MCT from 21 d of postnatal age to 49 d of postnatal age. Then, the piglets’ biochemical parameters and gene expressions related to energy metabolism and mitochondrial function were determined (n 4). Compared with NBW, IUGR decreased the ATP contents and succinate oxidation rates in the liver of piglets, and reduced hepatic mitochondrial citrate synthase (CS) activity (P<0·05). IUGR piglets exhibited reductions in hepatic mitochondrial DNA (mtDNA) contents and gene expressions related to mitochondrial biogenesis compared with NBW piglets (P<0·05). The MCT diet increased plasma ghrelin concentration and hepatic CS and succinate dehydrogenase activities, but decreased hepatic pyruvate kinase activity compared with the SO diet (P<0·05). The MCT-fed piglets showed improved mtDNA contents and PPARγ coactivator-1α expression in the liver (P<0·05). The MCT diet alleviated decreased mRNA abundance of the hepatic PPARα induced by IUGR (P<0·05). It can therefore be postulated that MCT may have beneficial effects in improving energy metabolism and mitochondrial function in weanling piglets.

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