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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