Redox Regulation of the Mitochondrial Quality Control Protease Oma1

Bohovych, Iryna; Dietz, Jonathan V.; Swenson, Samantha; Zahayko, Nataliya; Khalimonchuk, Oleh

doi:10.1089/ars.2018.7642

Cited by 19 publications

(13 citation statements)

References 43 publications

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“…MnSOD is the primary mitochondrial antioxidant that scavenges superoxide anion. Several studies suggest that mROS may be involved in OMA1 regulation or induce OMA1-dependent OPA1 proteolytic processing [ 43 , 44 ]. Based on these reports, we initially hypothesized that mROS induces OMA1-dependent OPA1 proteolytic processing during CS + RW.…”

Section: Resultsmentioning

confidence: 99%

Overexpression of MnSOD Protects against Cold Storage-Induced Mitochondrial Injury but Not against OMA1-Dependent OPA1 Proteolytic Processing in Rat Renal Proximal Tubular Cells

Tobacyk

MacMillan-Crow

2021

Antioxidants

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Kidneys from deceased donors undergo cold storage (CS) preservation before transplantation. Although CS is a clinical necessity for extending organ quality preservation, CS causes mitochondrial and renal injury. Specifically, many studies, including our own, have shown that the triggering event of CS-induced renal injury is mitochondrial reactive oxygen species (mROS). Here, we explored the role of OMA1-depedent OPA1 proteolytic processing in rat kidney proximal tubular epithelial (NRK) cells in an in vitro model of renal CS (18 h), followed by rewarming (6 h) (CS + RW). The involvement of mROS was evaluated by stably overexpressing manganese superoxide dismutase (MnSOD), an essential mitochondrial antioxidant enzyme, in NRK cells. Western blots detected rapid OPA1 proteolytic processing and a decrease in ATP-dependent cell viability in NRK cells subjected to CS + RW compared to control cells. Small interfering RNA (siRNA) knockdown of OMA1 reduced proteolytic processing of OPA1, suggesting that OMA1 is responsible for OPA1 proteolytic processing during CS + RW-induced renal injury. Overexpression of MnSOD during CS + RW reduced cell death, mitochondrial respiratory dysfunction, and ATP-dependent cell viability, but it did not prevent OMA1-dependent OPA1 processing. These data show for the first time that OMA1 is responsible for proteolytically cleaving OPA1 in a redox-independent manner during renal cell CS.

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Section: Resultsmentioning

confidence: 99%

Overexpression of MnSOD Protects against Cold Storage-Induced Mitochondrial Injury but Not against OMA1-Dependent OPA1 Proteolytic Processing in Rat Renal Proximal Tubular Cells

Tobacyk

MacMillan-Crow

2021

Antioxidants

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“…It is mediated by two highly conserved inner membrane space-exposed cysteine residues, cysteine 272 and cysteine 332, which can form disulfide bonds. These bonds maintain the structure of the Oma1 complex [99]. Data indicate that only thiol-containing reductants decrease the proteolytic activity of Oma1.…”

Section: Initiation Of Rcdmentioning

confidence: 89%

Redox-Mediated Post-Translational Modifications of Proteolytic Enzymes and Their Role in Protease Functioning

Petushkova

Zamyatnin

2020

Biomolecules

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Proteolytic enzymes play a crucial role in metabolic processes, providing the cell with amino acids through the hydrolysis of multiple endogenous and exogenous proteins. In addition to this function, proteases are involved in numerous protein cascades to maintain cellular and extracellular homeostasis. The redox regulation of proteolysis provides a flexible dose-dependent mechanism for proteolytic activity control. The excessive reactive oxygen species (ROS) and reactive nitrogen species (RNS) in living organisms indicate pathological conditions, so redox-sensitive proteases can swiftly induce pro-survival responses or regulated cell death (RCD). At the same time, severe protein oxidation can lead to the dysregulation of proteolysis, which induces either protein aggregation or superfluous protein hydrolysis. Therefore, oxidative stress contributes to the onset of age-related dysfunction. In the present review, we consider the post-translational modifications (PTMs) of proteolytic enzymes and their impact on homeostasis.

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“…ROMO1 is one of the most critical mitochondrial membrane proteins that can contribute to the regulation and production of ROS, as well as the protection of the mitochondrial membrane and its structure [26]. The overexpression of ROMO1 has been shown in different disorders, especially cancer.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of reactive oxygen species modulator 1 is associated with advanced grades of bladder cancer

et al. 2020

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Reactive Oxygen Species Modulator 1 (ROMO1) plays a pivotal role in the regulation of mitochondrial structure integrity, and the production of reactive oxygen species (ROS). Increased ROMO1 expression was reported in various cancer cell lines; however, the possible association between ROMO1 expression and bladder cancer was not well studied. The present study aimed to investigate the rate of ROMO1 expression and the correlation of oxidative stress with the development of bladder cancer. In this study, a total of 35 cancerous and healthy adjacent tissues were examined using quantitative real-time polymerase chain reaction (qRT-PCR) to analyze the gene expression of ROMO1. Also, we evaluated the serum level of ROMO1 and Total Antioxidant Capacity (TAC), as well as Total Oxidant Status (TOS) in patients with bladder cancer along with age-and sex-matched healthy individuals. The ROMO1 gene was significantly higher in cancerous tissues than that of adjacent healthy tissues. Also, the serum levels of ROMO1, TAC, TOS, and Oxidative Stress Index (OSI) were increased in patients with bladder cancer compared with healthy subjects. It can be concluded that the overexpression of the ROMO1 gene is associated with advanced grades of bladder cancer as well as an increase in oxidative stress conditions. Our findings also suggest that the serum level of ROMO1 might be a promising tumor marker for bladder cancer.

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Redox Regulation of the Mitochondrial Quality Control Protease Oma1

Cited by 19 publications

References 43 publications

Overexpression of MnSOD Protects against Cold Storage-Induced Mitochondrial Injury but Not against OMA1-Dependent OPA1 Proteolytic Processing in Rat Renal Proximal Tubular Cells

Overexpression of MnSOD Protects against Cold Storage-Induced Mitochondrial Injury but Not against OMA1-Dependent OPA1 Proteolytic Processing in Rat Renal Proximal Tubular Cells

Redox-Mediated Post-Translational Modifications of Proteolytic Enzymes and Their Role in Protease Functioning

Overexpression of reactive oxygen species modulator 1 is associated with advanced grades of bladder cancer

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