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The functions, disease-related dysfunctions, and therapeutic targeting of neuronal mitochondria / edited by Valentin K. Gribkoff, Elizabeth A. Jonas, J. Marie Hardwick. -- Hoboken, New Jersey : John Wiley & Sons, c2016. – (58.1782 /F979) |
Contents
Contributors
SECTION I
MITOCHONDRIAL STRUCTURE AND ION CHANNELS
1 Mitochondrial
Permeability Transition: A Look From a Different Angle
1.1
Regulation of Intracellular Calcium in Neurons
1.2 Calcium
Overload and Mitochondrial Permeability Transition
1.3 The
Mitochondrial Transition Pore
Acknowledgments
References
2 The
Mitochondrial Permeability Transition Pore, the c-Subunit of the F1F0ATP
Synthase, Cellular Development, and Synaptic Efficiency
2.1
Introduction
2.2
Mitochondria at the Center of Cell Metabolism and Cell Death
2.3
Mitochondrial Inner Membrane Leak: Regulator of Metabolic Rate and
Uncoupling
2.4
Mitochondrial Inner Membrane Channels and Exchangers are Necessary for
Ca2+ Cycling and Cellular Ca2+ Dynamics
2.5
Mitochondrial Inner and Outer Membrane Channel Activity Regulates Ca2+
Re-Release from Mitochondria after Buffering
2.6 Bcl-2
Family Proteins Regulate Pathological Outer Mitochondrial Membrane
Permeabilization (MOMP)
2.7
Pathological Inner Membrane Depolarization: Mitochondrial Permeability
Transition
2.8 The
Quest for an Inner Membrane Ca2+-Sensitive Uncoupling Channel: The PT Pore
2.9 The
mPTP: A Molecular Definition
2.10 Closing of the mPTP May Enhance Mitochondrial
Metabolic Plasticity and Regulate Synaptic Properties in Hippocampal Neurons
2.11 mPTP
Opening Correlates with Cell Death in Acute Ischemia, ROS Damage, or Glutamate
Excitotoxicity
2.12
Pro-Apoptotic Proteolytic Cleavage Fragment of Bcl-xL Causes Large
Conductance Mitochondrial Ion Channel Activity Correlated with Hypoxic Synaptic
Failure: Outer Mitochondrial Channel Membrane Activity Alone or mPTP?
2.13
Synaptic Responses Decline during Long-Term Depression in Association
with Bcl-2 Family-Regulated Mitochondrial Channel Activity
2.14 Synapse
Loss During Neurodegenerative Disease May Require Mitochondrial Channel
Activity
2.15
Conclusions
Acknowledgments
References
3 Mitochondrial
Channels in Neurodegeneration
3.1
Introduction
3.2
Mitochondrial Channels in the Healthy Neuron
3.3
Mitochondrial Channels in the Dying Cell
3.4
Mitochondrial Channels in Neurodegenerative Diseases
3.5
Conclusions
References
SECTION II
CONTROL OF MITOCHONDRIAL SIGNALING NETWORKS
4
Mitochondrial Ca2+ Transport in the Control of Neuronal Functions:
Molecular and Cellular Mechanisms
103
4.1
Introduction
4.2
Physiological and Pharmacological Characteristics of Mitochondrial Ca2+
Transport in Neurons
4.3
Molecular Components of Mitochondrial Ca2+ Transport in Neurons
4.4
Mitochondrial Ca+ Signaling and Neuronal Excitability
4.5
Mitochondrial Ca2+ Cycling in the Regulation of Synaptic Transmission
4.6
Mitochondrial Ca2+ Transport and the Regulation of Gene Expression in
Neurons
4.7 Future
Directions
Acknowledgments
References
5 AMP-Activated
Protein Kinase (AMPK) as a Cellular Energy Sensor and Therapeutic Target for
Neuroprotection 130
5.1
Introduction
5.2
Conclusion and Future Perspectives
References
6 HDAC6: A
Molecule with Multiple Functions in Neurodegenerative Diseases
6.1 Introduction
6.2
Molecular Properties of HDAC6
6.3 HDAC6
and Neurodegenerative Diseases
6.4
Perspectives
References
7 Neuronal
Mitochondrial Transport
7.1
Introduction
7.2 Complex
Motility Patterns of Axonal Mitochondria
7.3
Mechanisms of Mitochondrial Transport
7.4
Mechanisms of Axonal Mitochondrial Anchoring
7.5
Regulation of Mitochondrial Transport by Synaptic Activity
7.6
Mitochondrial Transport and Synaptic Transmission
7.7
Mitochondrial Transport and Presynaptic Variability
7.8
Mitochondrial Transport and Axonal Branching
7.9
Mitochondrial Transport and Mitophagy
7.10 Conclusions and New Challenges
Acknowledgments
References
8 Mitochondria
in Control of Hypothalamic Metabolic Circuits
8.1
Introduction
8.2
Yin-Yang Relationship between Components of Hypothalamic Feeding and
Satiety Circuits
8.3
Mitochondria and Their Dynamics
8.4
Metabolic Principles of Hunger and Satiety Promotion: Mitochondria in
Support of Fat Versus Glucose Utilization
8.5
Mitochondria Dynamics and Cellular Energetics
8.6
Mitochondrial Dysfunction and Metabolic Disorders
8.7
Conclusions
References
9 Mitochondria
Anchored at the Synapse
9.1
Introduction
9.2
Calibrated Positioning of Mitochondria
9.3
Mitochondria and Crista Structure
9.4
Adhering Junctions and Linkages to the Cytoskeleton
9.5
Linkages of the OMM to the Mitochondrial Plaque and Reticulated Membrane
9.6
Functions of the Organelle Complex
9.7 MACs
and Filamentous Contacts: A Continuum of Structure?
Acknowledgments
References
SECTION III
DEFECTIVE MITOCHONDRIAL DYNAMICS AND MITOPHAGY 219
10 Neuronal Mitochondria are Different: Relevance
to Neurodegenerative Disease
10.1
Introduction
10.2
Mitochondrial Dynamics in Neurons and Neurodegenerative Disease
10.3 Triggering
Mitophagy in Neurons versus Other Cell Types
10.4 BCL-xL:
The Guardian of Mitochondria
Acknowledgments
References
11 PINK1 as a Sensor for Mitochondrial Function:
Dual Roles
11.1
Introduction
11.2 PINK1
Promotes Mitochondrial Function
11.3 Healthy
Mitochondria Import and Process PINK1
11.4
Accumulation of Full Length-PINK1 as a Sensor of Mitochondrial
Dysfunction
11.5
Cytosolic PINK1 as a Sensor for Mitochondrial Function
11.6 PINK1
and Mitochondrial Dynamics
11.7 Dual
Roles for PINK1 as a Sensor of Mitochondrial Function and Dysfunction
References
12 A Get-Together to Tear It Apart: The
Mitochondrion Meets the Cellular Turnover Machinery
12.1 Mitochondrial Quality Control in
Neurodegeneration
12.2 An Overview of the Ubiquitin-Proteasome System
12.3 Activities of the Cytosolic Proteasome at the
Outer Mitochondrial Membrane
12.4 The Turnover of Whole Mitochondria by
Mitophagy
12.5
Proteasomes and Phagophores Converge in the PINK1/Parkin Pathway
12.6
Implications of PINK1-/Parkin-Dependent Mitophagy in the Brain and in PD
12.7
Emerging Mitochondrial Quality Control Mechanisms
References
13 Mitochondrial Involvement in Neurodegenerative
Dementia
13.1
Introduction
13.2
Mitochondrial Dysfunction in Alzheimer Disease
13.3
Mitochondrial Dysfunction, Bioenergetic Deficits, and Oxidative Stress
in AD
13.4
Mitochondrial Fragmentation in AD
13.5
Synaptic Mitochondria in AD
13.6
Mitochondrial Dysfunction and Cationic Dyshomeostasis in AD
13.7
Mitochondrial Dysfunction in DLB
13.8 LRRK2
Mutations, Mitochondria and DLB
13.9
Akinetic Crisis in Synucleinopathies is Linked to Genetic Mutations
Involving Mitochondrial Proteins
13.10
Conclusions
References
SECTION IV
MITOCHONDRIA-TARGETED THERAPEUTICS AND MODEL SYSTEMS
14 Neuronal Mitochondria as a Target for the
Discovery and Development of New Therapeutics
14.1 Neurodegenerative Disorders and the Status of
Drug Discovery
14.2 Mitochondria as Targets for the Development of
New NDD Therapies
14.3 The Effects of Dexpramipexole on Mitochondrial
Conductances An Example of an Approach for ALS and Other NDDs
14.4 What
is the Future of a Mitochondrial Approach for NDD Therapy?
Acknowledgments
References
15 Mitochondria as a Therapeutic Target for
Alzheimer's Disease
15.1
Introduction
15.2 Mitochondrial
Abnormalities and Dysfunction in Alzheimer's Disease
15.3
Mitochondria as a Drug Target
15.4 Conclusions
Acknowledgments
References
16 Mitochondria in Parkinson's Disease
16.1
Introduction
16.2 Role of
Mitochondria in Sporadic PD
16.3 Mitochondrial
Dysfunction in Monogenic PD
16.4
Conclusions
References
17 Therapeutic Targeting of Neuronal Mitochondria
in Brain Injury
17.1
Introduction
17.2
Mitochondria Bioenergetics
17.3
Traumatic Brain Injury
17.4
Pharmaceutical Interventions
17.5
Conclusion
References
18 The Use of Fibroblasts from Patients with
Inherited Mitochondrial Disorders for Pathomechanistic Studies and Evaluation
of Therapies
18.1
Introduction
18.2
Pathomechanistic Studies of Mitochondrial Disorders in Patients' Fibroblasts
18.3
Evaluation of Therapeutic Options Using Patient Derived Fibroblasts
18.4
Conclusion
Acknowledgments
References
Index
