The Impact of Oxidative Stress on Ribosomes: From Injury to Regulation

Shcherbik, Natalia; Pestov, Dimitri G.

doi:10.3390/cells8111379

Cited by 81 publications

(76 citation statements)

References 163 publications

(203 reference statements)

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“…Here we demonstrate that Fe 2+ can damage RNA, and the ribosome, by two separate and distinct mechanisms. The first mechanism is the well-known Fenton reaction (22) whereby the reaction of Fe 2+ with O 2 or H 2 O 2 generates hydroxyl radicals, causing oxidative damage of nucleic acids (25-29). A second, non-oxidative mechanism of Fe 2+ -mediated RNA damage can be more extensive in some conditions than oxidative damage.…”

Section: Introductionmentioning

confidence: 99%

Cutting in-line with iron: ribosomal function and non-oxidative RNA cleavage

Guth-Metzler

Bray

Frenkel-Pinter

et al. 2019

Preprint

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5Divalent metal cations are essential to the structure and function of the ribosome. Previous 2 6 characterizations of ribosome structure and function performed under standard laboratory 2 7conditions have implicated Mg 2+ as the primary mediator of ribosomal structure and function. 8The contribution of Fe 2+ as a ribosomal cofactor has been largely overlooked, despite the 2 9 ribosome's evolution in a high Fe 2+ environment, and its continued use by obligate anaerobes 3 0 inhabiting high Fe 2+ niches. Here we show that (i) iron readily cleaves RNA by a non-oxidative 3 1 mechanism that has not been detected previously, (ii) functional ribosomes purified from cells 3 2 grown under low O 2 , high Fe 2+ conditions are associated with Fe 2+ , (iii) a small subset of Fe 2+ 3 3that is associated with the ribosome is not exchangeable with surrounding cations, presumably 3 4 because they are highly coordinated by rRNA. In total, these results expand the ancient role of 3 5 iron in biochemistry, suggest a novel method for regulation of translation by iron, and highlight a 3 6 possible new mechanism of iron toxicity. 3 7

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Section: Introductionmentioning

confidence: 99%

Cutting in-line with iron: ribosomal function and non-oxidative RNA cleavage

Guth-Metzler

Bray

Frenkel-Pinter

et al. 2019

Preprint

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“…As our understanding of the global role of ubiquitination expands from a degradation signal to a modulator of a vast array of cellular pathways, a deeper review of ribosome ubiquitination gives insight into the multiple roles ubiquitin can play within translation control. In the past ten years, several regulatory mechanisms of translational control by ubiquitination of ribosomes have been explored, including the control of ribosome abundance [49], quality control at the ribosome [128], and the translational response to oxidative stress [65,165]. Within these mechanisms, we have discussed how ubiquitin participates in changing ribosomal structure, impacting interactions with ribosome binding factors, and signaling to degrade various components of the ribosome.…”

Section: Discussionmentioning

confidence: 99%

“…Although H 2 O 2 is required to induce RTU by regulating the activity of selective K63 ubiquitin enzymes [65], we are only in the beginning of understanding the complexity of translation regulation during stress. As mentioned before, oxidative stress can impact translation at several steps of the process, including initiation, elongation, and quality control [50,164,165]. Recent work by the Zaher lab showed that RNA alkylating and oxidizing agents, MMS and 4-NQO, respectively, can lead to ribosome stalling and increased Ltn1-dependent ubiquitination of the arrested peptide, in addition to ubiquitination of ribosomal proteins mediated by the RQC E3 Hel2 [194].…”

Section: Overview Of Redox Control Of Translation By Ubiquitin (Rtu) mentioning

confidence: 96%

“…During oxidative stress, eukaryotic cells accumulate large amounts of ubiquitinated proteins [65,159], and much of the earlier research was focused on the degradation role of ubiquitin in the removal of oxidatively damaged proteins [159][160][161][162][163]. Although protein degradation is an important mechanism to control ribosome abundance (discussed in Section 3), more recent work has focused on the non-degradative role ubiquitin plays in translational regulation under oxidative stress [50,164,165].…”

Section: Role Of Ubiquitin In Oxidative Stress Responsementioning

confidence: 99%

“…Synthesis of new proteins is often halted or decreased due to risks associated with high ROS, including protein damage, toxic gain-of-function, and aggregation [168]. ROS-driven modification of ribosomal proteins and rRNA alters the function and efficiency of the ribosomes, as extensively reviewed by Shcherbik and Pestov [165]. These modifications include the K48 polyubiquitination of ribosomal proteins, which leads to their degradation by the canonical UPS [163].…”

Section: Translational Control Under Oxidative Stressmentioning

confidence: 99%

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Expanding Role of Ubiquitin in Translational Control

Dougherty

Maduka

Inada

et al. 2020

IJMS

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The eukaryotic proteome has to be precisely regulated at multiple levels of gene expression, from transcription, translation, and degradation of RNA and protein to adjust to several cellular conditions. Particularly at the translational level, regulation is controlled by a variety of RNA binding proteins, translation and associated factors, numerous enzymes, and by post-translational modifications (PTM). Ubiquitination, a prominent PTM discovered as the signal for protein degradation, has newly emerged as a modulator of protein synthesis by controlling several processes in translation. Advances in proteomics and cryo-electron microscopy have identified ubiquitin modifications of several ribosomal proteins and provided numerous insights on how this modification affects ribosome structure and function. The variety of pathways and functions of translation controlled by ubiquitin are determined by the various enzymes involved in ubiquitin conjugation and removal, by the ubiquitin chain type used, by the target sites of ubiquitination, and by the physiologic signals triggering its accumulation. Current research is now elucidating multiple ubiquitin-mediated mechanisms of translational control, including ribosome biogenesis, ribosome degradation, ribosome-associated protein quality control (RQC), and redox control of translation by ubiquitin (RTU). This review discusses the central role of ubiquitin in modulating the dynamism of the cellular proteome and explores the molecular aspects responsible for the expanding puzzle of ubiquitin signals and functions in translation.Int. J. Mol. Sci. 2020, 21, 1151 2 of 24 initiation, elongation, and termination, with each being fundamental processes conserved across all organisms [20][21][22]. These steps require the proper binding of both RNA and protein factors, and regulation is often facilitated by the alteration of these binding patterns. As ribosomes are highly abundant and responsible for all protein synthesis within the cell, even minor changes to binding patterns could have a large impact on global protein production and cellular health, depending on which steps of translation are altered. Mutations and dysregulation of translational control can lead to a variety of diseases such as cancer, neurological disorders, bone marrow dysfunction and immunodeficiency, among others [23]. As translation is a core process in maintaining cellular function and health, dysfunctional regulation can have devastating results for the cell.Translational control does not occur in a universal manner across a single cell, but varies based on ribosomal subpopulations, with functions specific to cellular localization, transcript targeting, and signaling pathways [24,25]. These subpopulations are distinguishable by RNA and ribosomal protein composition [26,27], binding factors [28], intracellular localization [29,30], and post-translational modifications (PTM) [31]. These subpopulations have a differential capacity to bind and interact with both mRNA and protein factors required for active transla...

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Dual‐Responsive Nanocomposites for Synergistic Antibacterial Therapies Facilitating Bacteria‐Infected Wound Healing

Cheng

et al. 2022

Adv Healthcare Materials

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The rising dangers of bacterial infections have created an urgent need for the development of a new generation of antibacterial technologies and therapeutics. Antibacterial photodynamic therapy (PDT), considered as a noninvasive treatment with no drug resistance, has become a new promising photochemistry‐involved treatment strategy. Titanium oxide (TiO2) is proved to be a very efficient PDT agent among the photosensitive materials, while the property of a large bandgap of TiO2 makes it only be excited by ultraviolet light, which is harmful to organisms. In this work, a novel ligand‐to‐metal charge transfer (LMCT) mediated TiO2 PDT strategy is proposed via the harmless near‐infrared light irradiation. By choosing a mussel‐inspired material, polydopamine (PDA) is involved in forming mesoporous TiO2@PDA nanoparticles (mTiO2@PDA NPs). The catechol groups of PDA can attach the TiO2 tightly even in colloidal environments, and can also form the LMCT bridge, exciting TiO2 to exert PDT function via 808 nm irradiation. Combining the sonodynamic therapy (SDT) of TiO2 and the photothermal therapy properties of PDA, this simple structure mTiO2@PDA enables synergistic antibacterial applications with multiple functions under the dual excitation of NIR and ultrasound. This reliable all‐in‐one NPs can achieve great antibacterial effect and a rapid repair of infected wounds.

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The Impact of Oxidative Stress on Ribosomes: From Injury to Regulation

Cited by 81 publications

References 163 publications

Cutting in-line with iron: ribosomal function and non-oxidative RNA cleavage

Cutting in-line with iron: ribosomal function and non-oxidative RNA cleavage

Expanding Role of Ubiquitin in Translational Control

Dual‐Responsive Nanocomposites for Synergistic Antibacterial Therapies Facilitating Bacteria‐Infected Wound Healing

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