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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Cell competition and the regulative nature of early mammalian development.
TL;DR: The mammalian embryo exhibits a remarkable plasticity that allows it to correct for the presence of aberrant cells, adjust its growth so that its size is in accordance with its developmental stage, or integrate cells of another species to form fully functional organs as mentioned in this paper .
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Protective effects of cannabidiol on the membrane proteins of skin keratinocytes exposed to hydrogen peroxide via participation in the proteostasis network.
TL;DR: In this article, the effects of cannabidiol (CBD), a phytocannabinoid known for its antioxidant and anti-inflammatory properties, on the proteome of keratinocyte membranes exposed to H2O2 were evaluated.
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Polymerase delta-interacting protein 38 (PDIP38) modulates the stability and activity of the mitochondrial AAA+ protease CLPXP.
Philip R. Strack,Erica J. Brodie,Erica J. Brodie,Hanmiao Zhan,Verena J. Schuenemann,Liz J. Valente,Liz J. Valente,Tamanna Saiyed,Bradley R. Lowth,Lauren M. Angley,Matthew A. Perugini,Matthew A. Perugini,Kornelius Zeth,Kornelius Zeth,Kaye N. Truscott,David A. Dougan +15 more
TL;DR: It is shown, that human PDIP38 is directed to the mitochondrion in a membrane potential dependent manner, where it resides in the matrix compartment, together with its partner protein CLPX, and is a bona fide adaptor protein for the mitochondrial protease, CLPXP.
Journal ArticleDOI
Reduced endosomal microautophagy activity in aging associates with enhanced exocyst‐mediated protein secretion
Gregory J. Krause,Antonio Diaz,Maryam Jafari,Rabia R. Khawaja,Esperanza Agullo-Pascual,Olaya Santiago-Fernández,Alicia L. Richards,Kuei-Ho Chen,Phillip Dmitriev,Yan Sun,Stephanie K. See,Kotb Abdelmohsen,Krystyna Mazan-Mamczarz,Nevan J. Krogan,Myriam Gorospe,Danielle L. Swaney,S. Sidoli,Jose Javier Bravo-Cordero,Martin Kampmann,Ana Maria Cuervo +19 more
TL;DR: It is shown that activity of endosomal microautophagy (eMI), a selective type of autophagy occurring in late endosomes, declines with age and the sub‐proteome affected by this loss of function is identified and identified.
Journal ArticleDOI
Nrf2, stress and aging
TL;DR: To regulate metabolic processes in order to produce energetic molecules as well as on their capacity to mount anti-stress responses, complex co-regulation and wiring of cell-aut autonomous and non-autonomous mechanisms are required.
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
TL;DR: It is demonstrated that Nrf2 is essential for the transcriptional induction of phase II enzymes and the presence of a coordinate transcriptional regulatory mechanism for phase II enzyme genes and the nrf2-deficient mice may prove to be a very useful model for the in vivo analysis of chemical carcinogenesis and resistance to anti-cancer drugs.
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Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy
Sue C. Bodine,Esther Latres,Susanne Baumhueter,Venus Lai,Lorna Nunez,Brian A. Clarke,William Poueymirou,Frank J. Panaro,Erqian Na,Kumar Dharmarajan,Zhen-Qiang Pan,David M. Valenzuela,Thomas M. DeChiara,Trevor Stitt,George D. Yancopoulos,David J. Glass +15 more
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.