Molecular Nutrition and Mitochondria: Metabolic Deficits, Whole-Diet Interventions, and Targeted Nutraceuticals

Front Cover
Molecular Nutrition and Mitochondria
Copyright Page
Contents
List of contributors
Preface
Acknowledgments
1 Mitochondria as a target in experimental and clinical nutrition
1 Targeting mitochondrial dysfunction with nutrients: challenges and opportunities
1.1 Introduction
1.2 Diseases involving mitochondrial dysfunction
1.3 Targeting mitochondrial dysfunction with nutrients
1.3.1 Vitamins and cofactors
1.3.1.1 Quinone-based vitamins and coenzymes
1.3.1.2 Vitamin E
1.3.1.3 Vitamin C
1.3.1.4 Vitamins B
1.3.2 Endogenous antioxidants
1.3.2.1 Glutathione
1.3.2.2 N-Acetylcycteine
1.3.2.3 Lipoic acid
1.3.3 Endogenous metabolites and transporters
1.3.3.1 Creatine
1.3.3.2 Carnitine
1.3.4 Dietary fatty acids
1.3.4.1 Omega-3 polyunsaturated fatty acids
1.3.5 Carotenoids
1.3.6 Ginsenosides
1.3.7 Polyphenols
1.3.7.1 Phenolic acids
1.3.7.2 Flavonoids
1.3.7.3 Stilbenoids
1.3.7.4 Curcuminoids
1.3.8 Isothiocyanates
1.3.8.1 Sulforaphane
1.4 Challenges and limitations of using nutrients to target mitochondrial dysfunction
1.5 Topical use of nutrients for dermo-cosmetic applications
1.6 Conclusion and perspectives
References
2 Mitochondrion at the crossroads between nutrients and the epigenome
2.1 Introduction
2.2 Epigenetic modifications
2.2.1 DNA methylation
2.2.2 Histone modifications and chromatin remodeling
2.2.3 Noncoding RNA
2.3 Mitochondrial epigenetics and mito-epigenetics
2.3.1 Mitochondrial epigenetics: how mitochondria affect epigenetic pathways
2.3.1.1 Epigenetic regulations in the nucleus affect mitochondrial functions
2.3.1.2 Mitochondrial functions impact the nuclear epigenome
2.3.2 Mito-epigenetics: epigenetic regulations in the mitochondrial genome
2.3.2.1 mtDNA methylation
2.3.2.2 Mitochondrial transcription factor A and the mitochromosome structure
2.3.2.3 mitoMIRs
2.4 Impact of diet on the epigenome: the mediation of mitochondria
2.4.1 How diet modulates the epigenome
2.4.2 Focus on diet-related metabolic connections between mitochondria and cytoplasm able to affect the epigenome
2.4.2.1 Methyl donors, the one-carbon cycle and methylation reactions
2.4.2.2 Acetyl-coA and acetylation reactions
2.4.2.3 Antioxidants
2.4.3 Effects of nutrients and diet on mitochondrial epigenetics and mito-epigenetics
2.5 Conclusions
References
3 Nutritional assessment and malnutrition in adult patients with mitochondrial disease
3.1 Introduction
3.1.1 Gastro intestinal problems and BMI
3.1.2 Food intake
3.1.3 Prevalence of malnutrition in mitochondrial diseases
3.1.4 The optimal method for nutritional assessment in adult mitochondrial diseases patients
3.1.4.1 Nutritional assessment
3.1.4.2 Energy requirements
3.1.4.3 Body composition
3.1.4.4 Functional parameters
3.1.4.5 PG SGA
3.1.4.6 GLIM criteria
3.1.4.7 Sarcopenia
3.1.4.8 NRS_2002 screening tool
3.1.5 Sex differences
3.2 Nutritional assessment and dietary interventions
3.3 Conclusion
References
4 Therapeutic potential and metabolic impact of alternative respiratory chain enzymes
4.1 Introduction
4.2 Alternative oxidase
4.3 Alternative NADH dehydrogenase
4.4 Transgenic models of alternative respiratory chain enzymes
4.4.1 Mammalian cell models
4.4.2 Drosophila melanogaster
4.4.3 Rodent models
4.5 Metabolic impact of alternative enzymes
4.5.1 Nutrition
4.5.2 Reactive oxygen species
4.6 Therapeutic potential of alternative enzymes in mitochondria-related diseases
References
2 Essential nutrients in mitochondrial nutrition
5 Aging, mitochondrial dysfunctions, and vitamin E
5.1 Introduction
5.1.1 Mitochondria, reactive oxygen species and the free radical theory of aging
5.1.2 Mitocondrial DNA and aging
5.1.3 Mitochondrial dynamics, mitophagy and aging
5.1.4 Retrograde signaling: from mitochondria to nucleus
5.1.5 Mitochondria and the “inflammaging”
5.2 Vitamin E
5.2.1 Vitamin E and antioxidant capacity
5.2.2 Uptake and cellular distribution of vitamin E
5.2.3 Vitamin E functions in mitochondria
5.2.4 Vitamin E, mitochondria, and aging
5.3 The necessity for an alternative theory
5.3.1 ROS signaling, aging, and lifespan
5.3.2 “The gradual ROS response hypothesis”
5.4 Concluding remarks
References
6 The role of B vitamins in protecting mitochondrial function
6.1 Introduction
6.2 B vitamins and mitochondrial metabolism
6.2.1 Vitamin B1 (thiamine)
6.2.2 Vitamin B2 (riboflavin)
6.2.3 Vitamin B3 (niacin)
6.2.4 Vitamin B5 (pantothenic acid)
6.2.5 Vitamin B6 (pyridoxal phosphate)
6.2.6 Vitamin B8/B7 (biotin)
6.2.7 Vitamin B11/B9 (folate)
6.2.8 Vitamin B12 (cobalamin)
6.3 Oxidative stress and mitochondrial toxicity: role of B vitamins
6.4 Role of B vitamins as mitochondrial nutrients
6.5 Mitochondrial signaling metabolites: impact of B vitamins
6.5.1 B vitamins and HIF1 signaling
6.5.2 Impacts of B vitamin on methylation of histone and DNA
6.5.3 B vitamin: as regulator of histone acetylation
References
7 Analysis of the mitochondrial status of murine neuronal N2a cells treated with resveratrol and synthetic isomeric resvera...
7.1 Introduction
7.2 Material and methods
7.2.1 Synthesis of aza-stilbenes I to VII
7.2.2 Cell culture and treatments
7.2.3 Measurement of cell viability with the fluorescein diacetate assay
7.2.4 Evaluation of adherent cells with crystal violet staining assay
7.2.5 Flow cytometric quantification of cells with depolarized mitochondria with DiOC6(3)
7.2.6 Flow cytometric measurement of mitochondrial reactive oxygen species production with MitoSOX-Red
7.2.7 Statistical analysis
7.3 Results
7.4 Discussion and conclusion
Acknowledgments
Conflict of interest
References
8 Dietary eicosapentaenoic acid and docosahexaenoic acid for mitochondrial biogenesis and dynamics
8.1 Introduction
8.2 Mitochondrial biogenesis and dynamics
8.2.1 Mitochondrial biogenesis
8.2.2 Mitochondrial dynamics
8.3 Effect of n-3 polyunsaturated fatty acids on mitochondrial biogenesis and dynamics
8.4 Conclusion
References
9 Vitamin C and mitochondrial function in health and exercise
9.1 Vitamin C (ascorbic acid, ascorbate)
9.2 Mitochondria
9.3 Mitochondria structure and roles
9.4 Vitamin C and the mitochondria
9.5 Mitochondriopathies
9.6 Role of vitamin C in mitochondrial disease
9.7 Safety of vitamin C
9.8 Vitamin C and exercise (physiology/inflammation/recuperation)
9.9 Vitamin C as an ergogenic factor (performance)
References
10 Roles of dietary fiber and gut microbial metabolites short-chain fatty acids in regulating mitochondrial function in cen...
10.1 Introduction
10.2 Gut microbiota and short-chain fatty acids
10.3 Short-chain fatty acids regulate peripheral organizational activities
10.4 Effects of short-chain fatty acids on modulating the central nervous system function
10.4.1 Short-chain fatty acids influence cognitive and psychological function on mitochondria in the brain
10.4.2 Short-chain fatty acids influence appetitive function on mitochondria in the brain
References
3 Dietary bioactive compounds and mitochondrial function
11 Mitochondria-targeted antioxidants: coenzyme Q10, mito-Q and beyond
11.1 Introduction
11.2 Importance of coenzyme Q in mitochondria
11.3 CoQ10 prevents oxidative damage
11.4 Structure of coenzyme Q and mitochondrial-targeted coenzyme Q-related compounds
11.5 Idebenone reduces reactive oxygen species levels and bypasses complex I-deficiency
11.6 MitoQ a strong antioxidant that protects against apoptosis and induces mitophagy
11.7 Pharmacokinetics of mitochondrial-targeted antioxidant
11.8 Therapeutic use of idebenone
11.8.1 Therapeutic use of idebenone in Friedreich ataxia
11.8.2 Idebenone treatment of leber hereditary optic neuropathy and other neuropathic diseases
11.8.3 Therapeutic use of idebenone in other oxidative-damage related diseases
11.9 Therapeutic activity of MitoQ
11.9.1 MitoQ use in inflammation and immune response
11.9.2 MitoQ as a treatment in neurodegenerative diseases
11.9.3 Rare diseases
11.9.4 Ischemia/reperfusion and organ transplantation
11.9.5 Liver fibrosis
11.9.6 Metabolic syndrome and related diseases
11.9.7 Therapeutic potential of MitoQ in the treatment of cardiovascular diseases
11.9.8 Other uses of MitoQ
11.10 Other mitochondria-targeted compounds
11.11 Conclusions
References
12 Flavonoids, mitochondrial enzymes and heart protection
12.1 Introduction
12.2 Mitochondria and mitochondrial enzymes in cellular functions
12.3 Mitochondria as an essential organelle for cardiovascular health
12.4 Role of mitochondrial enzymes in cardiomyocytes
12.4.1 Mitochondrial enzymes for scavenging reactive oxygen species
12.4.2 Mitochondrial enzymes for apoptosis in cardiomyocytes
12.4.3 Mitochondrial enzymes in autophagy
12.5 Structure and function of dietary flavonoids
12.6 Pharmacokinetic profile (ADME) of flavonoids
12.7 Structure activity relationship of flavonoids for cardioprotective activity
12.8 Biological action of flavonoids in cardioprotection
12.8.1 Antiplatelet activity
12.8.2 Antioxidant activity
12.8.3 Anti-inflammatory activity
12.8.4 Antihypertensive activity
12.8.5 Antiatherogenic activity
12.8.6 Hypoxia, necrotic and apoptotic activity
12.8.7 Mitophagy
12.9 Concluding remarks
References
13 Tea polyphenols stimulate mt bioenergetics in cardiometabolic diseases
13.1 An introduction to cardiometabolic diseases
13.2 Structure and bioenergetics of mitochondria
13.3 Mitochondria and its role in metabolism
13.4 Mitochondria and metabolic stress
13.5 Mitochondrial fission and fusion
13.6 Polyphenols as functional food
13.7 Tea and its health benefits
13.8 Cytoprotective actions of green tea polyphenols
13.9 Effects of nutraceuticals on cardiometabolic disorders
13.10 Molecular mechanisms of flavonoids in cardiometabolic diseases
13.11 Molecular mechanisms of action of tea polyphenols
References
14 A review of quercetin delivery through nanovectors: cellular and mitochondrial effects on noncommunicable diseases
14.1 Introduction
14.2 Quercetin metabolism, biodistribution and pharmacokinetics
14.3 Mechanism of protection of quercetin in noncommunicable diseases
14.3.1 Quercetin as an antioxidant compound
14.3.1.1 Effects of nanoquercetin in cardiovascular ischemia-reperfusion injury
14.3.1.2 Effects of nanoquercetin in prevention of gastric ulcers
14.3.1.3 Effect of nanoquercetin on sperm quality and fertility
14.3.2 Quercetin as an anticancer agent
14.3.2.1 Effects of nanoquercetin against tumor cells
14.4 Nanomaterials for quercetin encapsulation
14.5 Conclusions
Acknowledgments
References
15 Creatine monohydrate for mitochondrial nutrition
15.1 Creatine monohydrate
15.1.1 Structure
15.1.2 De novo synthesis of creatine
15.1.3 Supplementation form
15.1.4 Tissue distribution of creatine
15.1.5 Catabolism
15.2 Creatine in cellular and mitochondrial bioenergetics
15.2.1 Creatine kinase isoenzymes
15.2.2 The phosphocreatine “shuttle” system in cell energy homeostasis
15.3 Creatine/mitochondrial creatine kinase system in health and disease
15.3.1 In cardiac and skeletal muscles of athletes
15.3.1.1 Effects of creatine monohydrate on the skeletal muscle mitochondria
15.3.1.2 Effects of creatine monohydrate on the cardiac muscle mitochondria
15.3.2 In muscle disorders
15.3.2.1 Mitochondrial myopathy
15.3.2.2 Ischemia/infarction
15.3.2.3 Sarcoma and chemotherapy
15.3.3 In pregnancy and gestation
15.3.4 Creatine and central nervous system mitochondria
15.3.4.1 Creatine: the devoted energy provider for neuronal mitochondria
15.3.4.2 Creatine, mitochondrial bioenergetics, and neurodegenerative disorders
15.3.4.3 Creatine, neuronal mitochondrial dysfunction, and amyotrophic lateral sclerosis
15.3.4.4 Creatine, neuronal mitochondrial dysfunction, and multiple sclerosis
15.3.4.5 Creatine treatment and mitochondria: could it be the hope for patients with Parkinson’s disease?
15.3.5 Creatine and adipocyte-specific functions of the mitochondria
15.3.5.1 Creatine metabolism in adipose tissue
15.3.5.2 Creatine and obesity
15.4 A promising future
References
16 Arginine and neuroprotection: a focus on stroke
16.1 Introduction
16.2 Mitochondrial angiopathy in MELAS
16.3 Endothelial dysfunction in MELAS
16.4 Neuroimaging of stroke-like episodes in MELAS
16.5 Clinical study of L-arginine in MELAS
16.6 Superacute intervention by L-arginine
16.7 Therapeutic regimen of L-arginine for MELAS
16.8 Contraindication in the treatment of MELAS
16.9 Concluding remarks
16.10 Applications to other neurological conditions
16.11 Key facts of arginine and neuroprotection: a focus on stroke
16.11.1 Key fact of neuroprotection in MELAS
16.12 Summary points
References
17 Nutraceuticals for targeting NAD+ to restore mitochondrial function
17.1 Nicotinamide adenine dinucleotide as redox cofactor and signaling molecule in mitochondria
17.2 Cellular and mitochondrial nicotinamide adenine dinucleotide metabolism
17.3 Nicotinamide adenine dinucleotide and mitochondrial function
17.4 Nicotinamide adenine dinucleotide supplementation in human diseases
17.5 Conclusion
References
18 Curcumin for protecting mitochondria and downregulating inflammation
18.1 Introduction
18.2 Inflammation and oxidative stress
18.3 Mitochondria and inflammation
18.4 Mitochondria and oxidative stress
18.5 Mitochondrial inflammation and oxidative stress in inflammatory-related diseases
18.6 Curcumin as antioxidant and antiinflammatory agent
18.7 Mitochondrial targeting for the reduction of oxidative stress and inflammation
18.8 Curcumin as a direct mitochondrial reactive oxygen species scavenger
18.9 Curcumin enhances mitochondrial antioxidants
18.10 Curcumin activates the Nrf2 signaling pathway and protects mitochondrial damage and oxidant generation
18.11 Targeting of mitochondrial uncoupling proteins by curcumin
18.12 Targeting of mitochondrial sirtuins by curcumin
18.13 Targeting of mitochondrial p66shc by curcumin
18.14 Conclusion
Conflict of interest
References
19 Dihydrogen as an innovative nutraceutical for mitochondrial viability
19.1 Introduction
19.2 Dietary sources of molecular hydrogen
19.3 Hydrogen-rich water and mitochondrial function
19.4 Other dietary and complementary interventions with hydrogen
19.5 Dihydrogen and mitochondria: molecular mechanisms
19.6 Open questions and future research
19.7 Conclusion
References
20 Fucoxantin and mitochondrial uncoupling protein 1 in obesity
20.1 Three types of adipocytes
20.2 The importance of uncoupling protein 1 in regulating energy homeostasis
20.3 Fucoxanthin and uncoupling protein 1
References
21 Rice bran extract for the prevention of mitochondrial dysfunction
21.1 Introduction
21.2 Role of mitochondrial function in disease
21.3 Rice bran extracts and the mitochondria
21.4 Health properties of rice bran constituents associated with mitochondrial function
21.4.1 Proteins, nonproteogenic amino acids and derivatives
21.4.2 Fats and oils
21.4.3 Carbohydrates
21.4.4 Fiber
21.4.5 Small molecule antioxidants
21.4.6 Plant-based pigments and organic compounds
21.4.7 Mitochondria-specific enzyme mimetics from food, administered either as monocomponent formulas or mitochondria-speci...
21.5 Conclusion
References
22 Silymarin as a vitagene modulator: effects on mitochondria integrity in stress conditions
22.1 Introduction
22.2 An integrated antioxidant defense system
22.3 Mitochondria as an important source of reactive oxygen species
22.4 Antioxidant properties of silymarin
22.5 Protective effects of silymarin on mitochondria
22.5.1 In vitro evidence
22.5.2 In vivo evidence
22.6 Effect of SM on vitagene expression
22.7 Application of silymarin in poultry
22.8 Conclusions
References
23 Buckwheat trypsin inhibitors: novel nutraceuticals for mitochondrial homeostasis
23.1 Introduction
23.2 Roles of mitochondrial proteases in maintaining mitochondrial homeostasis and deliberate regulation by protease inhibitors
23.2.1 Mitochondrial metabolisms and homeostasis
23.2.2 Proteases and their inhibitors are critical for health and mitochondrial homeostasis
23.3 Buckwheat, health benefits and presence of trypsin inhibitors
23.3.1 Buckwheat as a food staple in some regions and its global presence as a functional food
23.3.2 Potential health benefits from consuming buckwheat foods
23.3.3 Presence of buckwheat trypsin inhibitors, characteristics and physiological roles
23.4 Roles of mitochondrial homeostasis in healthy aging and improvement by presence of recombinant buckwheat trypsin inhibitor
23.4.1 Roles of mitochondrial homeostasis in healthy aging
23.4.2 Buckwheat trypsin inhibitor and recombinant buckwheat trypsin inhibitors: properties, functionality and their potent...
23.4.3 Potential future trends in research and studies
References
4 Whole-diet interventions and mitochondrial function
24 Diet restriction-induced mitochondrial signaling and healthy aging
24.1 Mitochondrial pathways induced by caloric restriction
24.1.1 Caloric restriction, inhibition of insulin/insulin-like growth factor-1 signaling insulin-like growth factor 1 pathw...
24.1.2 Caloric restriction, inhibition of target of rapamycin signaling, and mitochondria
24.1.3 Caloric restriction, sirtuin activation, and mitochondria
24.1.4 Caloric restriction, AMP-activated protein kinase activation, and mitochondria
24.1.5 Caloric restriction, PGC-1α activation, and mitochondria
24.1.6 Caloric restriction and mitochondrial signaling to the cell
24.1.7 Mitochondria-mediated tissue-specific effects of caloric restriction
24.1.7.1 Adipose tissue
24.1.7.2 Skeletal muscle
24.1.7.3 Liver
24.1.7.4 Brain
24.1.7.5 Heart and cardiovascular system
24.1.8 Effects of calorie restriction in mitochondrial biogenesis and energy metabolism in nonhuman primates and healthy humans
24.2 Mitochondrial mechanisms underlying health span extension by popular restrictive diet regimes in mammals
24.2.1 Ketogenic diet
24.2.2 Macronutrient restriction
24.2.3 Intermittent fasting
24.3 Mitochondrial pathways activated by caloric restriction mimetics
24.3.1 Multifunctional compounds: polyphenols and polyamines
24.3.1.1 Polyphenols
24.3.1.2 Polyamines
24.3.2 NAD+ precursors
24.3.3 AMP-activated protein kinase agonists
24.3.4 Mammalian target of rapamycin inhibitors
24.3.5 Mitochondrial uncouplers
24.4 Concluding remarks
Funding
References
25 Rejuvenation of mitochondrial function by time-controlled fasting
25.1 Introduction
25.2 Strategies employed to study the effects of time-controlled fasting
25.3 Time-controlled fasting and health
25.4 Effects of time-controlled fasting on mitochondrial function
25.5 Temporal caloric restriction effects on mitochondrial biogenesis
25.6 Fasting effects on mitochondrial dynamics and turnover
25.7 Effects on mitochondrial energy metabolism
25.8 Effects on reactive oxygen species handling
25.9 Effects on mitochondrial synthetic function
25.10 Fasting-mediated modulation of mitochondrial signaling
25.11 Adverse effects on mitochondrial function in response to fasting
25.12 Time-controlled fasting strategies to boost mitochondrial fidelity and disease amelioration
25.13 Fasting and other organelles
25.14 Conclusion
References
26 Dietary modulation and mitochondrial DNA damage
26.1 Introduction
26.2 Mitochondrial DNA damage accumulation and maintenance of the mitochondrial DNA
26.3 Caloric restriction and dietary restriction
26.4 Dietary components with the potential to activate the nutrient sensing pathways
26.5 Impact of high-fat diets on mitochondrial DNA
26.6 Fructose and ethanol as potential metabolic toxins
26.7 Conclusion
References
Index
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