Redox regulation of proteasome function

Lefaki, Maria; Papaevgeniou, Nikoletta; Chondrogianni, Niki

doi:10.1016/j.redox.2017.07.005

Cited by 85 publications

(63 citation statements)

References 100 publications

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“…Correspondingly, expression levels of certain subunits of the proteasome are induced in states of impaired gcat expression ( Figure 5A), and inversely, interference with expression of these proteasome subunit abolishes the effect of both gcat-RNAi and low-dose MGO on lifespan ( Figures 5B-5G). In full congruence with published evidence on these two transcription factors and their role in proteostatic response (Chondrogianni et al, 2015), also in response to ROS (Lefaki et al, 2017), epistasis analyses indicate that both HSF-1 and SKN-1 are required for the response to both gcat impairment and MGO per se. Interestingly, low-dose MGO even exerts toxic effects on nematodes in states of skn-1 impairment ( Figure 4C), but not hsf-1 impairment ( Figure 4G).…”

Section: Discussionsupporting

confidence: 77%

Impairing L-Threonine Catabolism Promotes Healthspan through Methylglyoxal-Mediated Proteohormesis

et al. 2018

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Whether and how regulation of genes and pathways contributes to physiological aging is topic of intense scientific debate. By performing an RNA expression-based screen for genes downregulated during aging of three different species, we identified glycine-C-acetyltransferase (GCAT, EC 2.3.1.29). Impairing gcat expression promotes the lifespan of C. elegans by interfering with threonine catabolism to promote methylglyoxal (MGO; CAS 78-98-8) formation in an amine oxidase-dependent manner. MGO is a reactive dicarbonyl inducing diabetic complications in mammals by causing oxidative stress and damaging cellular components, including proteins. While high concentrations of MGO consistently exert toxicity in nematodes, we unexpectedly find that low-dose MGO promotes lifespan, resembling key mediators of gcat impairment. These were executed by the ubiquitin-proteasome system, namely PBS-3 and RPN-6.1 subunits, regulated by the stress-responsive transcriptional regulators SKN-1/NRF2 and HSF-1. Taken together, GCAT acts as an evolutionary conserved aging-related gene by orchestrating an unexpected nonlinear impact of proteotoxic MGO on longevity.

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Section: Discussionsupporting

confidence: 77%

Impairing L-Threonine Catabolism Promotes Healthspan through Methylglyoxal-Mediated Proteohormesis

et al. 2018

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“…Modified proteins are degraded mainly by the proteasomal systems (20S and 26S) [ 44 ]. However, during oxidative stress, the activity of the 26S proteasome decreases, while the activity of the 20S proteasome remains mostly unchanged [ 45 ]. Unsurprisingly, in many inflammatory diseases, dysregulation of proteasomal activity is observed [ 35 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Reduced Proteasome Activity and Enhanced Autophagy in Blood Cells of Psoriatic Patients

Karabowicz

Wroński²,

Ostrowska

et al. 2020

IJMS

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Psoriasis is a skin disease that is accompanied by oxidative stress resulting in modification of cell components, including proteins. Therefore, we investigated the relationship between the intensity of oxidative stress and the expression and activity of the proteasomal system as well as autophagy, responsible for the degradation of oxidatively modified proteins in the blood cells of patients with psoriasis. Our results showed that the caspase-like, trypsin-like, and chymotrypsin-like activity of the 20S proteasome in lymphocytes, erythrocytes, and granulocytes was lower, while the expression of constitutive proteasome and immunoproteasome subunits in lymphocytes was increased cells of psoriatic patients compared to healthy subjects. Conversely, the expression of constitutive subunits in erythrocytes, and both constitutive and immunoproteasomal subunits in granulocytes were reduced. However, a significant increase in the autophagy flux (assessed using LC3BII/LC3BI ratio) independent of the AKT pathway was observed. The levels of 4-HNE, 4-HNE-protein adducts, and proteins carbonyl groups were significantly higher in the blood cells of psoriatic patients. The decreased activity of the 20S proteasome together with the increased autophagy and the significantly increased level of proteins carbonyl groups and 4-HNE-protein adducts indicate a proteostatic imbalance in the blood cells of patients with psoriasis.

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“…Based on the intricate network of ubiquitin-dependent quality control mechanisms, stressed or defective mitochondria often affect UPS activity, which largely relies on the abundance and activity of the 26S proteasome (Marshall and Vierstra, 2019). Central to this regulatory relationship are reactive oxygen species (ROS), that are generated inside mitochondria via oxidative phosphorylation (Lefaki et al, 2017). Changes in ROS level have been linked to reversible disassembly of the 26S proteasome into 20S and 19S subunits.…”

Section: Mitochondrial Stress Response Mechanismsmentioning

confidence: 99%

Mitochondrial Quality Control Governed by Ubiquitin

Ravanelli

Brave

Hoppe

2020

Front. Cell Dev. Biol.

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Mitochondria are essential organelles important for energy production, proliferation, and cell death. Biogenesis, homeostasis, and degradation of this organelle are tightly controlled to match cellular needs and counteract chronic stress conditions. Despite providing their own DNA, the vast majority of mitochondrial proteins are encoded in the nucleus, synthesized by cytosolic ribosomes, and subsequently imported into different mitochondrial compartments. The integrity of the mitochondrial proteome is permanently challenged by defects in folding, transport, and turnover of mitochondrial proteins. Therefore, damaged proteins are constantly sequestered from the outer mitochondrial membrane and targeted for proteasomal degradation in the cytosol via mitochondrial-associated degradation (MAD). Recent studies identified specialized quality control mechanisms important to decrease mislocalized proteins, which affect the mitochondrial import machinery. Interestingly, central factors of these ubiquitindependent pathways are shared with the ER-associated degradation (ERAD) machinery, indicating close collaboration between both tubular organelles. Here, we summarize recently described cellular stress response mechanisms, which are triggered by defects in mitochondrial protein import and quality control. Moreover, we discuss how ubiquitindependent degradation is integrated with cytosolic stress responses, particularly focused on the crosstalk between MAD and ERAD.

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Redox regulation of proteasome function

Cited by 85 publications

References 100 publications

Impairing L-Threonine Catabolism Promotes Healthspan through Methylglyoxal-Mediated Proteohormesis

Impairing L-Threonine Catabolism Promotes Healthspan through Methylglyoxal-Mediated Proteohormesis

Reduced Proteasome Activity and Enhanced Autophagy in Blood Cells of Psoriatic Patients

Mitochondrial Quality Control Governed by Ubiquitin

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