Biochemistry of Apoptosis and Autophagy

Dedication
Preface
Contents
Contributors
1 A Protein-Centric Perspective of Autophagy and Apoptosis Signaling and Crosstalk in Health and Disease
	Introduction and Rationale
	Signal Transduction Pathways
		Major Pathways of Autophagy
		Major Pathways of Apoptosis
	Crosstalk Between Autophagy and Apoptosis
		Atg Proteins [31]
		Caspases
		BH3-Only Proteins
		P53 Protein
	Clinical Relevance of Autophagy and Apoptosis
		Autophagy in the Pathogenesis of Four Organ Types
		Apoptosis in the Pathogenesis of Four Organ Types
		Crosstalk of Autophagy and Apoptosis in the Pathogenesis of Ischemia–reperfusion Injury
	Conclusions and Future Perspectives
	References
2 Adrenergic Receptor Signaling Pathways in the Regulation of Apoptosis and Autophagy in the Heart
	Introduction
	Adrenergic Receptors in the Heart
	Role of Adrenergic Receptor Signaling in the Regulation of Apoptosis and Autophagy in the Heart
	β-AR Blockers and Heart Disease
	New Mechanistic Insights for the Actions of β-AR Blockers in the Regulation of Apoptosis and Autophagy
	Conclusion
	References
3 Apoptosis in Ischemic Heart Disease
	Introduction
	Development of Apoptosis
		Mediator Proteins of the Extrinsic Apoptotic Pathway
		Mediator Proteins of the Intrinsic (Apoptotic) Pathway
		Mediator Proteins of the Terminal Apoptotic Pathway
	Targeting Apoptosis for the Treatment of IHD
	Conclusions
	References
4 Autophagy in Cardiac Physiology and Pathology
	Introduction
	The Necessity to Maintain Cardiomyocyte Health
	Biochemistry and Regulation of Autophagy
		The Different Types of Autophagy
		Regulation of Autophagy in Response to Stress Conditions
	The Role of Autophagy in Physiology and Pathology
	Autophagy and Cell Death
		Revisiting an Old Debate: Does Autophagic Cell Death Exist In Vivo?
		The Autophagy-Apoptosis Interplay
	Cardiac Autophagy in Physiology and Pathology
		The Necessary Role of Autophagy Throughout Cardiomyocyte Life
		Autophagy During Cardiac Atrophy
		Autophagy During Cardiac Hypertrophy
		Autophagy and Cardiac Proteinopathy
		Autophagy and Cardiac Ageing
	Concluding Remarks
	References
5 Caspase Signaling Pathways as Convenors of Stress Adaptation
	Introduction
	Cell Death and Apoptosis
	Caspase Signaling in Death and Nondeath Cell Function
	Stress Adaptations and the Involvement of Caspase Activity
		Hypertrophy
		Atrophy
	Caspase Signaling: At the Intersection Between Proteostasis and Autophagy
	Mechanisms that Restrain Caspase Activity: A Key Step in the Non-lethal Deployment of Caspase Proteases
	Conclusions
	References
6 Cross Talk Between Apoptosis and Autophagy in Regulating the Progression of Heart Disease
	Apoptosis in Heart Failure
		Extrinsic Pathway of Apoptosis
		Intrinsic Pathway of Apoptosis
		Endoplasmic Reticulum (ER) Mediated Intrinsic Apoptosis
		Apoptotic Mechanisms Independent of Caspases
	Protective Role of Apoptosis During Cardiac Development
	Autophagy
		Mechanisms Underlying Autophagy
		Role of Autophagy in Heart Failure
	Crosstalk Between Autophagy and Apoptosis
	Conclusion
	References
7 Fibroblasts, Fibrosis and Autophagy
	Introduction
	Immune Cells as Mediators of Fibrosis
		Mast Cells
		Macrophages
		Interleukins
	Autophagy
		Regulation of Autophagy by TGFβ
	Potential Therapeutic Targets for Fibrosis
	Conclusion
	References
8 Gene Therapy and Its Application in Cardiac Diseases
	Introduction
	Gene Therapy
		Different Options for Transgene Delivery
		Emerging Therapeutic Approaches
	Use of Gene Therapy Techniques for Treating Cardiac Fibrosis
	Conclusion
	References
9 Circadian Regulation of Autophagy in the Heart Via the mTOR Pathway
	Introduction
		Circadian and the Cardiovascular System
		The mTOR Pathway and the Cardiovascular System
		Circadian Mediated Mitochondrial Autophagy in the Cardiovascular System
		Interaction of Circadian Machinery and Cell Metabolism
		SIRT1 as a Potential Mediator Between Circadian Rhythm, mTOR, and the Cardiovascular System
		MTOR and Starvation
	References
10 Mitochondria and Their Cell Hosts: Best of Frenemies
	Attacking the Host: Apoptosis and MPTP
	MPTP: With Friends Like This, Who Needs Enemies?
	Anti-Apoptotic Defenses
	Freezing Out the Host: Energy Insufficiency
	Spreading Rumors: Creating Inflammation
	Unstable Allies: Fusion and Fission
	Defense: Isolate and Eliminate Troublemakers
	Conclusions
	Best of Frenemies
	References
11 Mitochondrial Dysfunction and Mitophagy: Physiological Implications in Cardiovascular Health
	Introduction
	PINK1/Parkin-Mediated Mitophagy
	Autophagy Adaptors
	Mitophagy Receptors
		BNIP3 and NIX
		FUNDC1
		Other Mitophagy Receptors
	Deubiquitinases as Critical Regulators of Mitophagy
	Coordination Between Mitochondrial Dynamics and Mitophagy
	Concluding Remarks
	References
12 Proteotoxicity and Autophagy in Neurodegenerative and Cardiovascular Diseases
	Introduction
	Protein Aggregation and Proteotoxicity
		Protein Amyloid Structures: Proteotoxic Oligomers
		Oligomer Structure and Toxicity
		Oligomers in Alzheimer’s Disease, TTR Amyloidosis, and AL Amyloidosis
	Proteotoxicity and Autophagy in Neurologic Diseases
		Alzheimer’s Disease
		Parkinson’s Disease
	Proteotoxicity and Autophagy in Cardiovascular Diseases
		AL Cardiac Amyloidosis
		Other Cardiomyopathies
	Conclusions
	References
13 Regulation of Cell Death Signaling Pathways in Cardiac Myocytes by Mitochondrial Bnip3
	Introduction
		Apoptosis and Necrosis Cell Death Pathways
		Bcl-2 Family and Molecular Regulation of Cell Death
		Mitochondrion Regulated Cell Death Pathways
		Hypoxia-Inducible Expression of Bnip3
		Bnip3 and Autophagy
		Bnip3 and Doxorubicin Cardiomyopathy
		Concluding Comments
	References
14 Role of Cardiomyocyte Apoptosis in Heart Failure
	Introduction
	Development of Cardiomyocytes Apoptosis in Heart Failure
	Cardiomyocyte Apoptosis in Volume Overload Induced Heart Failure
	Cardiomyocyte Apoptosis in Heart Failure Due to Dilated Cardiomyopathy
	Conclusions
	References
15 The Role of FGF2 isoforms in Cell Survival in the Heart
	General Introduction
	FGF2 Isoforms in Heart Pathophysiology
	Conclusion
	References