Shaping proteostasis at the cellular, tissue, and organismal level.
TLDR
This review by Morimoto and colleagues examines mechanisms by which protein homeostasis (proteostasis) is achieved in multicellular organisms and discusses the implications for health and disease.Abstract:
The proteostasis network (PN) regulates protein synthesis, folding, transport, and degradation to maintain proteome integrity and limit the accumulation of protein aggregates, a hallmark of aging and degenerative diseases. In multicellular organisms, the PN is regulated at the cellular, tissue, and systemic level to ensure organismal health and longevity. Here we review these three layers of PN regulation and examine how they collectively maintain cellular homeostasis, achieve cell type-specific proteomes, and coordinate proteostasis across tissues. A precise understanding of these layers of control has important implications for organismal health and could offer new therapeutic approaches for neurodegenerative diseases and other chronic disorders related to PN dysfunction.read more
Citations
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Journal ArticleDOI
The Protein Folding Problem: The Role of Theory.
TL;DR: The protein folding problem was first articulated as question of how order arose from disorder in proteins: How did the various native structures of proteins arise from interatomic driving forces encoded within their amino acid sequences, and how did they fold so fast? These matters have now been largely resolved by theory and statistical mechanics combined with experiments as mentioned in this paper.
Journal ArticleDOI
Cancer chemoprevention via activation of proteostatic modules
TL;DR: A synopsis of studies showing that proteostatic modules activation (e.g. by natural products) represents a promising tumour-chemopreventive approach to anti-ageing effects in model organisms is presented.
Journal ArticleDOI
Real-world clinical applicability of pathogenicity predictors assessed on SERPINA1 mutations in alpha-1-antitrypsin deficiency.
Edoardo Giacopuzzi,Mattia Laffranchi,Romina Berardelli,Viola Ravasio,Ilaria Ferrarotti,Bibek Gooptu,Giuseppe Borsani,Annamaria Fra +7 more
TL;DR: The potential of computational methods to provide meaningful predictions of the pathogenic significance of novel mutations and identify areas for further investigation in alpha‐1‐antitrypsin deficiency is highlighted.
Journal ArticleDOI
Mechanisms Linking Mitochondrial Dysfunction and Proteostasis Failure.
Bingwei Lu,Su Guo +1 more
TL;DR: Recent findings on mitochondrial outer membrane-associated mRNA translation are examined, how this process is sensitive to mitochondrial dysfunction and constantly surveyed by ribosome-associated quality control (RQC), and how defects in this process generate aberrant proteins with unusual C-terminal extensions that promote aggregation and drive proteostasis failure.
Book ChapterDOI
Cellular Metabolism and Aging
TL;DR: This review will outline how cellular biochemistry and energy homeostasis change during aging, and highlight protein quality control, mitochondria, epigenetics, nutrient-sensing pathways, as well as the interplay between these systems with respect to their impact on cellular health.
References
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The Ubiquitin System
Avram Hershko,Aaron Ciechanover +1 more
TL;DR: This review discusses recent information on functions and mechanisms of the ubiquitin system and focuses on what the authors know, and would like to know, about the mode of action of ubi...
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The Unfolded Protein Response: From Stress Pathway to Homeostatic Regulation
Peter Walter,David Ron +1 more
TL;DR: The vast majority of proteins that a cell secretes or displays on its surface first enter the endoplasmic reticulum, where they fold and assemble, and only properly assembled proteins advance from the ER to the cell surface.
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An nrf2/small maf heterodimer mediates the induction of phase ii detoxifying enzyme genes through antioxidant response elements
Ken Itoh,Tomoki Chiba,Satoru Takahashi,Tetsuro Ishii,Kazuhiko Igarashi,Yasutake Katoh,Tatsuya Oyake,Norio Hayashi,Kimihiko Satoh,Ichiro Hatayama,Masayuki Yamamoto,Yo-ichi Nabeshima +11 more
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Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy
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TL;DR: Two genes encode ubiquitin ligases that are potential drug targets for the treatment of muscle atrophy, and mice deficient in either MAFbx orMuRF1 were found to be resistant to atrophy.