Protein homeostasis and molecular chaperones in aging

Arslan, Mehmet Alper; Csermely, Péter; Sőti, Csaba

doi:10.1007/s10522-006-9053-7

Cited by 36 publications

(27 citation statements)

References 43 publications

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“…The proteome is maintained by various mechanisms, all of which show an age-dependent decline (36). During heat stress, chaperones are up-regulated, but this mechanism fails with age (37,38). Proteasome activity also declines with age (39).…”

Section: Discussionmentioning

confidence: 99%

Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage

Azpurua

Chen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

142

118

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The naked mole-rat (Heterocephalus glaber) is a subterranean eusocial rodent with a markedly long lifespan and resistance to tumorigenesis. Multiple data implicate modulation of protein translation in longevity. Here we report that 28S ribosomal RNA (rRNA) of the naked mole-rat is processed into two smaller fragments of unequal size. The two breakpoints are located in the 28S rRNA divergent region 6 and excise a fragment of 263 nt. The excised fragment is unique to the naked mole-rat rRNA and does not show homology to other genomic regions. Because this hidden break site could alter ribosome structure, we investigated whether translation rate and amino acid incorporation fidelity were altered. We report that naked mole-rat fibroblasts have significantly increased translational fidelity despite having comparable translation rates with mouse fibroblasts. Although we cannot directly test whether the unique 28S rRNA structure contributes to the increased fidelity of translation, we speculate that it may change the folding or dynamics of the large ribosomal subunit, altering the rate of GTP hydrolysis and/or interaction of the large subunit with tRNA during accommodation, thus affecting the fidelity of protein synthesis. In summary, our results show that naked mole-rat cells produce fewer aberrant proteins, supporting the hypothesis that the more stable proteome of the naked mole-rat contributes to its longevity.aging | NMR

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Section: Discussionmentioning

confidence: 99%

Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage

Azpurua

Chen

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

142

118

View full text Add to dashboard Cite

show abstract

“…The imbalance in overall protein homeostasis is a crucial factor in the development of heritable age‐related neurodegenerative diseases and during normal aging (Dobson, 2003; Vacher et al ., 2005; Zhang et al ., 2005; Arslan et al ., 2006; Haass & Selkoe, 2007; Morimoto, 2008). Achieving and maintaining the correct three‐dimensional protein structure is a continuous struggle within cells.…”

Section: Introductionmentioning

confidence: 99%

Specific protein homeostatic functions of small heat‐shock proteins increase lifespan

et al. 2015

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SummaryDuring aging, oxidized, misfolded, and aggregated proteins accumulate in cells, while the capacity to deal with protein damage declines severely. To cope with the toxicity of damaged proteins, cells rely on protein quality control networks, in particular proteins belonging to the family of heat‐shock proteins (HSPs). As safeguards of the cellular proteome, HSPs assist in protein folding and prevent accumulation of damaged, misfolded proteins. Here, we compared the capacity of all Drosophila melanogaster small HSP family members for their ability to assist in refolding stress‐denatured substrates and/or to prevent aggregation of disease‐associated misfolded proteins. We identified CG14207 as a novel and potent small HSP member that exclusively assisted in HSP70‐dependent refolding of stress‐denatured proteins. Furthermore, we report that HSP67BC, which has no role in protein refolding, was the most effective small HSP preventing toxic protein aggregation in an HSP70‐independent manner. Importantly, overexpression of both CG14207 and HSP67BC in Drosophila leads to a mild increase in lifespan, demonstrating that increased levels of functionally diverse small HSPs can promote longevity in vivo.

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“…Uncoupling of the organelle network becomes especially important after stress, as it prevents the spread of damage (e.g., in the form of free radicals) from one organelle to the other. Moreover, chaperones may act as an automatic switch to accomplish this task, since during stress, when the amount of misfolded proteins becomes much higher, chaperones become occupied by misfolded proteins, which leads to the dissociation of their original partners [15,17,83,84, M.T. Nguyen and C. S ti unpublished observations], and causes -among many other consequences -the 'automatic' de-coupling of chaperone mediated inter-organelle contacts.…”

Section: Position and Dynamics Of Molecular Chaperones In Protein-promentioning

confidence: 99%

System Level Mechanisms of Adaptation, Learning, Memory Formation and Evolvability: The Role of Chaperone and Other Networks

Gyurko

Sőti

Steták

et al. 2014

CPPS

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During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here, we describe first the protein structure networks of molecular chaperones, then characterize chaperone containing sub-networks of interactomes called as chaperone-networks or chaperomes. We review the role of molecular chaperones in short-term adaptation of cellular networks in response to stress, and in long-term adaptation discussing their putative functions in the regulation of evolvability. We provide a general overview of possible network mechanisms of adaptation, learning and memory formation. We propose that changes of network rigidity play a key role in learning and memory formation processes. Flexible network topology provides 'learningcompetent' state. Here, networks may have much less modular boundaries than locally rigid, highly modular networks, where the learnt information has already been consolidated in a memory formation process. Since modular boundaries are efficient filters of information, in the 'learning-competent' state information filtering may be much smaller, than after memory formation. This mechanism restricts high information transfer to the 'learning competent' state. After memory formation, modular boundary-induced segregation and information filtering protect the stored information. The flexible networks of young organisms are generally in a 'learning competent' state. On the contrary, locally rigid networks of old organisms have lost their 'learning competent' state, but store and protect their learnt information efficiently. We anticipate that the above mechanism may operate at the level of both protein-protein interaction and neuronal networks.

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Protein homeostasis and molecular chaperones in aging

Cited by 36 publications

References 43 publications

Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage

Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage

Specific protein homeostatic functions of small heat‐shock proteins increase lifespan

System Level Mechanisms of Adaptation, Learning, Memory Formation and Evolvability: The Role of Chaperone and Other Networks

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