1st Edition

Proteostasis and Proteolysis

  • Available for pre-order. Item will ship after November 23, 2021
ISBN 9780367499327
November 23, 2021 Forthcoming by CRC Press
304 Pages 25 Color & 28 B/W Illustrations

USD $120.00

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Book Description

Proteostasis integrates biological pathways controlling biogenesis, trafficking, folding, and degradation of proteins. This book focuses on two protein breakdown/degradation processes (proteolysis), which are part of a normally functioning proteostatic system: the ubiquitin-proteasome system and autophagy.

Table of Contents

Chapter 1 Ribosomal Pauses during Translation and Proteostasis

Alejandro Ferrando, Alihamze Fathinajafabadi, Arantxa Martínez-Férriz and Rosa Farràs

1 Introduction

2 Irreversible ribosomal stalling and the RQC pathway

3 Reversible ribosomal pauses

3.1 eIF5A rescues poly-Pro stalling motifs

3.2 Translational pauses during protein folding, organellar targeting and protein complex assembly

4 Concluding remarks


Chapter 2 Protein folding and misfolding: Deciphering mechanisms of age-related diseases

Judith-Elisabeth Riemer, Diana Panfilova, Heidi Olzscha

1 Introduction

1.1 Kinetic and thermodynamic aspects of protein folding

2 Molecular chaperones

2.1 Definition of the term molecular chaperone

2.2 Significance of molecular chaperones in the cell

2.3 A network of molecular chaperones

2.4 Functions of molecular chaperones and interplay with other protein quality control systems

3 Protein misfolding

3.1 Process of protein misfolding

3.2 Factors leading to protein misfolding

4 Age-related proteinopathies

4.1 Systemic proteinopathies

4.2 Localized proteinopathies

5 Current and future treatments

6 Conclusions


Chapter 3 Transcriptional regulation of proteostatic mechanisms

Marianna Kapetanou, Sophia Athanasopoulou, Efstathios S. Gonos

1 Introduction

2 Transcriptional regulation of proteome integrity

2.1 The Heat Shock Response

2.2 Oxidative Stress Response

2.3 Unfolded Protein Response

3 Transcriptional regulation of protein degradation

3.1 Ubiquitin-Proteasome System

3.2 Autophagy

4 Crosstalk between proteostatic mechanisms

5 Conclusions and perspectives


Chapter 4 MicroRNAs as central regulators of adult myogenesis and proteostasis loss in skeletal muscle aging

Ioannis Kanakis, Ioanna Myrtziou, Aphrodite Vasilaki, Katarzyna Goljanek-Whysall

1 Introduction

2 Biogenesis and regulatory function of miRs

3 Myogenesis in adulthood and sarcopenia

4 miRs role in adult myogenesis

4.1 Skeletal muscle-specific miRs-myomiRs

4.2 miR effects on satellite cells

4.3 myomiRs-1, 133 and -206 effects on skeletal muscle cells

4.4 miR involvement in signaling pathways

5 miRs in Skeletal Muscle Ageing and Sarcopenia

5.1 Differential expression of miRs in young and old skeletal muscle

5.2 miR-181a regulates skeletal muscle aging

5.3 miR-dependent regulation of longevity-related SIRT1 in aged skeletal muscle

6 Proteostasis loss and autophagy regulation by miRs in aged skeletal muscle

7 Conclusions and future perspectives


Chapter 5 mRNA granules and proteostasis in aging and age-related diseases

Fivos Borbolis and Popi Syntichaki

1 Introduction

2 Definitions and components of PBs and SGs

2.1 P-bodies (PBs)

2.2 Stress Granules (SGs)

3 Proteostatic functions of PBs and SGs

3.1 In stress: the more stable, the less worrying

3.2 In aging and disease: the more unstable, the less worrying

4 Regulation of mRNA granules by proteostatic mechanisms

5 mRNA granules-based potential interventions in aging and age-related diseases

6 Concluding remarks


Chapter 6 Phospholipids and the unfolded protein response

Ilias Gkikas and Nektarios Tavernarakis

1 Introduction

2 Regulation of ER and mitochondrial UPR

2.1 The UPRER signaling

2.2 The UPRmt signaling

3 Phospholipid biosynthesis in the ER and Mitochondria

3.1 Phosphatidylcholine

3.2 Phosphatidylethanolamine

3.3 Phosphatidylserine

3.4 Phosphatidylinositol

3.5 Phosphatidylglycerol

3.6 Cardiolipin

4 Phospholipids and UPR signaling

4.1 UPR as a sensor of phospholipid bilayer stress

4.2 UPR as a regulator of phospholipid abundance

5 Conclusions


Chapter 7 Ubiquitin Ligases involved in progeroid syndromes and age-associated pathologies

Lisa Fechtner and Thorsten Pfirrmann

1 Introduction

2 The Ubiquitin modification system

2.1 Ubiquitin ligases

2.2 Ubiquitin ligases involved in progeroid syndromes

2.3 Ubiquitin ligases involved in age-associated pathologies

2.4 Aging-associated ubiquitin ligase genes

3 Outlook and conclusions


Chapter 8 Role of SUMOylation in neurodegenerative diseases and inflammation

Esmeralda Parra-Peralbo, Veronica Muratore, Orhi Barroso-Gomila, Ana Talamillo, James D. Sutherland, Rosa Barrio

1 Introduction

2 SUMO in neurodegenerative diseases

2.1 Alzheimer’s Disease

2.2 Parkinson’s Disease

2.3 Polyglutamine diseases

3 SUMO in inflammation

4 Inflammation in neurodegenerative diseases

5 Concluding remarks


Chapter 9 NEDD8 and oxidative stress

Elah Pick and Giovanna Serino

1 Introduction

2 The cellular redox state and its effect on Ubl enzyme activity

3 The NEDD8/Rub1 catalytic cascade of enzymes is sensitive to ROS

4 The COP9 signalosome Cullin deNEDDylase and ROS

5 CRL substrates that play a role in the anti-oxidant response

5.1 HIF-1α

5.2 NRF2

5.3 FNIP1

5.4 NPR1

6 Non-cullin NEDD8 substrates and their response to stress

7 Concluding remarks


Chapter 10 Structure, function and regulators of the 20S proteasome

Tobias Jung and Annika Höhn

1 Introduction

2 Structure, function and substrates of the 20S complex

3 Ubiquitination

4 Regulators of the 20S proteasome

4.1 The 19S regulatory complex (PA700)

4.2 The 11S regulatory complex

4.3 The PA200 regulator

5 Tissue specific proteasomes

6 Conclusion


Chapter 11 Cellular responses to proteasome impairment

Maja Studencka-Turski and Elke Krüger

1 Introduction

2 Consequences of diminished proteasome activity on the ER homeostasis

3 Activation of the TCF11/Nrf1 in response to proteasome impairment

4 Response of mTOR signaling to decreased proteasome activity

5 Induction of the innate immune response upon proteasome impairment

6 Concluding remarks


Chapter 12 Proteasome fate in aging and proteinopathies

Mary A. Vasilopoulou, Nikoletta Papaevgeniou, Niki Chondrogianni

1 Introduction

2 Protective mechanisms of protein quality control

2.1 Synthesis

2.2 Protein Folding

2.3 Protein degradation

3 Proteinopathies

3.1 Alzheimer’s disease

3.2 Parkinson’s disease

3.3 Huntington’s disease

3.4 Amyotrophic lateral sclerosis

4 Conclusions


Chapter 13 The Proteasomal System in Cancer

Sema Arslan Eseryel, Ulkugul Guven, Betul Karademir Yilmaz

1 Introduction

2 The UPS in cancer

3 Role of proteasome in cancer-related pathways

4 Regulation of cancer related signaling molecules by the proteasomal system

4.1 NF-κB

4.2 p53

4.3 p44 / 42 MAPK

4.4 Pro-apoptotic Bcl-2 gene family members

4.5 AP-1

5 Proteasome inhibitors

5.1 20S Proteasome inhibitors

5.2 Clinical studies

6 Targeting ubiquitination in cancer treatment

7 Conclusion


Chapter 14 Proteostasis and skin aging

Anne-Laure Bulteau and Bertrand Friguet

1 Hallmarks of skin aging

2 Role of mitochondrial proteases in skin aging

3 Age-associated impairment of autophagy in skin

4 Impairment of proteasome in skin aging and photoaging

5 Conclusions


Chapter 15 Reactive Oxygen Species and Protein Homeostasis in Skeletal Muscle Regeneration

Sofia Lourenço dos Santos, Aurore L’honoré, Isabelle Petropoulos

1 Introduction

2 Skeletal muscle regeneration

3 Redox homeostasis: ROS production, scavenging and signaling

4 Redox regulation of satellite cells in quiescence, regeneration, aging and pathological conditions

4.1 Redox regulation of satellite cell quiescence

4.2 Redox regulation of satellite cell function during regeneration

4.3 Redox regulation of satellite cell function during aging

4.4 Redox regulation of satellite cell function in muscular dystrophies

4.5 Redox regulation of satellite cell function in cachexia

5. Protein homeostasis: a new player in the regulation of skeletal muscle regeneration

5.1 The role of the unfolded protein response in satellite cell function

5.2 The role of the ubiquitin-proteasome system in satellite cell function

5.3 The role of autophagy in satellite cell function

6 Conclusion and perspectives


Chapter 16 Protein Degradation in Cardiac Health and Disease

Xuejun Wang

1 Introduction

2 The UPS in PQC

3 Clinical evidence of UPS dysfunction in cardiac pathogenesis

4 Occurrence of PFI in animal models of heart disease

5 PFI plays a major pathogenic role in a range of heart diseases

6 Mechanisms underlying cardiac PFI pathogenesis

7 Exploitation of proteasome phosphoregulation to target PFI in heart disease

7.1 PKA-mediated priming of cardiac proteasomes

7.2 PKG-mediated priming of cardiac proteasomes

7.3 Priming the proteasome by duo-activation of PKA and PKG to target cardiac PFI

8 Concluding remarks


Chapter 17 Autophagy in aging and oxidative stress

Dimitra Ranti, Anna Gioran, Niki Chondrogianni

1 Introduction

2 Autophagy: A bulk degradation system

2.1 The three types of autophagy

2.2 The steps and main molecular players of macroautophagy

2.3 Signaling in autophagy

3 Autophagy in oxidative stress

3.1 Reactive Oxygen Species and oxidative stress

3.2 ROS signaling and autophagy modulation

3.3 Autophagy-dependent regulation of ROS production and antioxidant mechanisms

4 Autophagy and aging

4.1 Introduction in aging

4.2 Autophagy in aging

4.3 Autophagy in longevity

5 Concluding remarks and future perspectives


Chapter 18 Autophagy in aging and longevity exemplified by the aging heart

Steffen Häseli and Christiane Ott

1 Introduction

2 Cardiac manifestation of the aging process

3 Autophagy is downregulated in the aging heart

3.1 Impairment of autophagic regulatory signaling during cardiac aging

3.2 Mitophagy and the aging heart

4 Conclusion


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Niki Chondrogianni

Research areas: Ageing, longevity, age-related diseases, proteolysis, proteasome, redox regulation, cellular senescence, C. elegans

Dr. Chondrogianni graduated and obtained her PhD from the Department of Biology of the National and Kapodistrian University of Athens in Greece, while she was a visiting fellow at the Universities Paris 7 in France and Bristol in UK. She conducted her post-doctoral studies at the National Hellenic Research Foundation (NHRF) in Athens focusing on the role of proteasome activation on cellular and organismal lifespan extension. She was trained in the use of C. elegans at the Foundation of Research and Technology-Hellas, Institute of Molecular Biology and Biotechnology in Greece. She established her lab at NHRF in 2009. She focuses on the genetic and environmental factors that govern ageing, longevity and age-related diseases with emphasis on proteasome regulation. She is seeking for natural or chemically-synthesized compounds that may act as proteasome activators and thus may serve as anti-ageing agents and/or as anti-aggregation compounds that can decelerate the progression of various proteinopathies with emphasis on Alzheimer’s disease.

Elah Pick

Research areas: Cell biology, protein biochemistry, proteolysis, redox, the ubiquitin proteasome system

Prof. Elah Pick performed her graduate and postdoctoral training in cell Biochemistry, membrane traffic and protein degradation at the Technion – Israel Institute of Technology. She performed a second postdoctoral training at Yale university on a family of genes that regulate the molecular and biochemical mechanisms responsible for cellular responses to external stimuli and stresses. She established her own lab in Israel, at the department for Biology and Environment of the University of Haifa, located at Oranim. Her lab investigates the effect of metabolic and environmental stresses such as oxidation, on the regulation of protein degradation.

Anna Gioran

Research areas: Mitochondria, neurobiology, metabolism proteostatic mechanisms, C. elegans

Dr. Anna Gioran carried out her graduate training at the German Center of Neurodegenerative Diseases (DZNE) in Bonn, Germany. During this time, she studied the effects of mitochondrial deficiency on the morphology of the nematode’s neurons. In her first postdoctoral fellowship she continued at the DZNE and she focused more on mitochondrial deficiencies and specifically on their metabolic implications and manners to rescue its detrimental effects at organismal level. At the time this book was written, she was conducting her second postdoctoral research under the supervision of Dr. Niki Chondrogianni at the National Hellenic Research Foundation in Athens, Greece, focusing on the interplay between proteostatic mechanisms and mitochondrial function.