Tissue-specific effects of temperature on proteasome function

Pispa, Johanna; Matilainen, Olli; Holmberg, Carina I.

doi:10.1007/s12192-020-01107-y

Cited by 13 publications

(23 citation statements)

References 34 publications

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“…Our previous research has demonstrated that UPS activity varies in a tissue-specific manner in live C. elegans , and is affected by aging and stress, such as proteasomal impairment and elevated growth temperature [ 31 , 32 , 35 ]. The rate of autophagic flux has also been reported to vary in different C. elegans tissues [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…NL2099[ rrf-3(pk1426)II ] mutant strain was a kind gift from Dr. G. Wong (University of Eastern Finland). YD116[ rrf-3(pk1426);xzIs2[unc-54p::UIM2::ZsProSensor] ] reporter strain was generated by crossing NL2099[ rrf-3(pk1426)II ] strain with YD114[ xzIs2[unc-54p::UIM2::ZsProSensor] ] [ 35 ]. Information on the cloning of the plasmid has been described previously in Matilainen et al, 2013, as a precursor for the YD90[ xzIs1[vha-6p::UIM2::ZsProSensor] ] strain [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

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Tissue-Specific Impact of Autophagy Genes on the Ubiquitin–Proteasome System in C. elegans

Jha

Holmberg

2020

Cells

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The ubiquitin–proteasome system (UPS) and the autophagy–lysosomal pathway (ALP) are the two main eukaryotic intracellular proteolytic systems involved in maintaining proteostasis. Several studies have reported on the interplay between the UPS and ALP, however it remains largely unknown how compromised autophagy affects UPS function in vivo. Here, we have studied the crosstalk between the UPS and ALP by investigating the tissue-specific effect of autophagy genes on the UPS at an organismal level. Using transgenic Caenorhabditis elegans expressing fluorescent UPS reporters, we show that the downregulation of the autophagy genes lgg-1 and lgg-2 (ATG8/LC3/GABARAP), bec-1 (BECLIN1), atg-7 (ATG7) and epg-5 (mEPG5) by RNAi decreases proteasomal degradation, concomitant with the accumulation of polyubiquitinated proteasomal substrates in a tissue-specific manner. For some of these genes, the changes in proteasomal degradation occur without a detectable alteration in proteasome tissue expression levels. In addition, the lgg-1 RNAi-induced reduction in proteasome activity in intestinal cells is not dependent on sqst-1/p62 accumulation. Our results illustrate that compromised autophagy can affect UPS in a tissue-specific manner, and demonstrate that UPS does not function as a direct compensatory mechanism in an animal. Further, a more profound understanding of the multilayered crosstalk between UPS and ALP can facilitate the development of therapeutic options for various disorders linked to dysfunction in proteostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Tissue-Specific Impact of Autophagy Genes on the Ubiquitin–Proteasome System in C. elegans

Jha

Holmberg

2020

Cells

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“…Surprisingly, a change in ambient temperature from 20 to 25°C can affect selective protein degradation via the UPS. UPS activity increases in the intestine but not in muscle cells, suggesting tissue-specific regulation of protein degradation ( Pispa et al, 2020 ). Increasing temperature conditions also modulates mRNA translation.…”

Section: The Influence Of Temperature On Proteostasismentioning

confidence: 99%

Temperature-Dependent Regulation of Proteostasis and Longevity

Vakkayil

Hoppe

2022

Front. Aging

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Temperature is an important environmental condition that determines the physiology and behavior of all organisms. Animals use different response strategies to adapt and survive fluctuations in ambient temperature. The hermaphrodite Caenorhabditis elegans has a well-studied neuronal network consisting of 302 neurons. The bilateral AFD neurons are the primary thermosensory neurons in the nematode. In addition to regulating thermosensitivity, AFD neurons also coordinate cellular stress responses through systemic mechanisms involving neuroendocrine signaling. Recent studies have examined the effects of temperature on altering various signaling pathways through specific gene expression programs that promote stress resistance and longevity. These studies challenge the proposed theories of temperature-dependent regulation of aging as a passive thermodynamic process. Instead, they provide evidence that aging is a well-defined genetic program. Loss of protein homeostasis (proteostasis) is one of the key hallmarks of aging. Indeed, proteostasis pathways, such as the heat shock response and aggregation of metastable proteins, are also controlled by thermosensory neurons in C. elegans. Prolonged heat stress is thought to play a critical role in the development of neurodegenerative protein misfolding diseases in humans. This review presents the latest evidence on how temperature coordinates proteostasis and aging. It also discusses how studies of poikilothermic organisms can be applied to vertebrates and provides new therapeutic strategies for human disease.

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“…The heat-shock-stressed cells also contained a 2-fold higher amount of the proteasome activator 11S, and the extent of the bound activator was doubled in early-and mid-passage cells only. Recent studies showed that C. elegans exhibits tissue-specific responses of the ubiquitin-proteasome system (UPS) as an organismal strategy to cope with a rise in ambient temperature [90]. An ambient temperature shift from 20 to 25 • C increased UPS activity in the intestine but not in the body wall muscle tissue, where a concomitant accumulation of polyubiquitinated proteins occurred.…”

Section: Effect Of Temperature Variationmentioning

confidence: 99%

Proteasome Biology: Chemistry and Bioengineering Insights

Račková

Csekes

2020

Polymers

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Proteasomal degradation provides the crucial machinery for maintaining cellular proteostasis. The biological origins of modulation or impairment of the function of proteasomal complexes may include changes in gene expression of their subunits, ubiquitin mutation, or indirect mechanisms arising from the overall impairment of proteostasis. However, changes in the physico-chemical characteristics of the cellular environment might also meaningfully contribute to altered performance. This review summarizes the effects of physicochemical factors in the cell, such as pH, temperature fluctuations, and reactions with the products of oxidative metabolism, on the function of the proteasome. Furthermore, evidence of the direct interaction of proteasomal complexes with protein aggregates is compared against the knowledge obtained from immobilization biotechnologies. In this regard, factors such as the structures of the natural polymeric scaffolds in the cells, their content of reactive groups or the sequestration of metal ions, and processes at the interface, are discussed here with regard to their influences on proteasomal function.

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Tissue-specific effects of temperature on proteasome function

Cited by 13 publications

References 34 publications

Tissue-Specific Impact of Autophagy Genes on the Ubiquitin–Proteasome System in C. elegans

Tissue-Specific Impact of Autophagy Genes on the Ubiquitin–Proteasome System in C. elegans

Temperature-Dependent Regulation of Proteostasis and Longevity

Proteasome Biology: Chemistry and Bioengineering Insights

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