Lifespan extension by peroxidase and dual oxidase-mediated ROS signaling through pyrroloquinoline quinone in <i>C. elegans</i>

Sasakura, Hiroyuki; Moribe, Hiroki; Nakano, Masahiko; Ikemoto, Kazuto; Takeuchi, Kosei; Mori, Ikue

doi:10.1242/jcs.202119

Cited by 35 publications

(39 citation statements)

References 120 publications

(180 reference statements)

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“…Furthermore, Duox are expressed in the respiratory and gastrointestinal tract in mammals [ 28 ], where they potentially could function as a host defense mechanism against infections similar as in Drosophila [ 29 , 30 ] and zebrafish [ 31 ]. In C. elegans , Duox function is also important for tyrosine crosslinking [ 32 ], immunity [ 33 ], oxidative stress resistance [ 13 , 34 ], and healthy aging [ 13 , 35 ] ( Figure 1 ). Here, I discuss how the C. elegans Duoxs become activated, and how the generated ROS acts in redox signaling to adapt to oxidative stress and re-establish cellular homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Redox Signaling of NADPH Oxidases Regulates Oxidative Stress Responses, Immunity and Aging

Ewald

2018

Antioxidants

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An accumulating body of evidence suggests that transient or physiological reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases act as a redox signal to re-establish homeostasis. The capacity to re-establish homeostasis progressively declines during aging but is maintained in long-lived animals to promote healthy aging. In the model organism Caenorhabditis elegans, ROS generated by dual oxidases (Duox) are important for extracellular matrix integrity, pathogen defense, oxidative stress resistance, and longevity. The Duox enzymatic activity is tightly regulated and under cellular control. Developmental molting cycles, pathogen infections, toxins, mitochondrial-derived ROS, drugs, and small GTPases (e.g., RHO-1) can activate Duox (BLI-3) to generate ROS, whereas NADPH oxidase inhibitors and negative regulators, such as MEMO-1, can inhibit Duox from generating ROS. Three mechanisms-of-action have been discovered for the Duox/BLI-3-generated ROS: (1) enzymatic activity to catalyze crosslinking of free tyrosine ethyl ester in collagen bundles to stabilize extracellular matrices, (2) high ROS bursts/levels to kill pathogens, and (3) redox signaling activating downstream kinase cascades to transcription factors orchestrating oxidative stress and immunity responses to re-establish homeostasis. Although Duox function at the cell surface is well established, recent genetic and biochemical data also suggests a novel role for Duoxs at the endoplasmic reticulum membrane to control redox signaling. Evidence underlying these mechanisms initiated by ROS from NADPH oxidases, and their relevance for human aging, are discussed in this review. Appropriately controlling NADPH oxidase activity for local and physiological redox signaling to maintain cellular homeostasis might be a therapeutic strategy to promote healthy aging.

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Section: Introductionmentioning

confidence: 99%

Redox Signaling of NADPH Oxidases Regulates Oxidative Stress Responses, Immunity and Aging

Ewald

2018

Antioxidants

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“…Both crh-1 RNAi and loss of jun-1 are reported to change the worm lifespan. 32,33 However, no evidence shows the expression levels of crh-1 and jun-1 decline during aging, similar to OGT-1. These results imply that CRH-1 and JUN-1 might modulate the lifespan via other targets, but not activation of OGT-1.…”

Section: Discussionmentioning

confidence: 99%

ELT‐2 promotes O‐GlcNAc transferase OGT‐1 expression to modulate Caenorhabditis elegans lifespan

Zhao

et al. 2020

J of Cellular Biochemistry

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O-GlcNAc transferase (OGT) is the enzyme catalyzing protein O-GlcNAcylation by addition of a single O-linked-β-N-acetylglucosamine molecule (O-GlcNAc) to nuclear and cytoplasmic targets, and it uses uridine diphosphate-Nacetylglucosamine (UDP-GlcNAc) as a donor. As UDP-GlcNAc is the final product of the nutrient-sensing hexosamine signaling pathway, overexpression or knockout of ogt in mammals or invertebrate models influences cellular nutrientresponse signals and increases susceptibility to chronic diseases of aging. Evidence shows that OGT expression levels decrease in tissues of older mice and rats. However, how OGT expression is modulated in the aging process remains poorly understood. In Caenorhabditis elegans, the exclusive mammalian OGT ortholog OGT-1 is crucial for lifespan control. Here, we observe that worm OGT-1 expression gradually reduces during aging. By combining prediction via the "MATCH" algorithm and luciferase reporter assays, GATA factor ELT-2, the homolog of human GATA4, is identified as a transcriptional factor driving OGT-1 expression. Chromatin immunoprecipitation-quantitative polymerase chain reaction and electrophoretic mobility shift assays show ELT-2 directly binds to and activates the ogt-1 promoter. Knockdown of elt-2 decreases the global O-GlcNAc modification level and reduces the lifespan of wild-type worms. The reduction in lifespan caused by elt-2 RNA interference is abrogated by the loss of ogt-1. These results imply that GATA factors are able to activate OGT expression, which could be beneficial for longevity and the development of therapeutic treatment for aging-related diseases.

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“…elegans that carry a mutation in either the BLI-3 peroxidase domain (n529) or NADPH oxidase domain (im10) are extremely short-lived. These two mutants show a lifespan reduction of about 20-60% compared to wild type either on live or on heatkilled OP50 E. coli food source [35,38]. It is worth pointing out that the standard OP50 E. coli used as a food source to culture C. elegans is a little bit pathogenic during aging.…”

Section: Bli-3-generated Ros Redox Signaling To Skn-1 To Promote Longmentioning

confidence: 96%

“…Since bli-3 is needed for protection against pathogens, the lifespan results on heat-killed OP50 E. coli indicate a functional role of BLI-3 during aging. The BLI-3 peroxidase domain mutant (e767) has been reported to be long-lived in one study [35] and short-lived in another [38]. Because bli-3 is important for collagen crosslinking and molting during development, the altered adult lifespan might be a consequence of developmental defects of reduced bli-3 function.…”

Section: Bli-3-generated Ros Redox Signaling To Skn-1 To Promote Longmentioning

confidence: 99%

“…By contrast, activating BLI-3 function either by redox co-factor pyrroloquinoline quinone (PQQ) [35], inhibiting memo-1 [13], or by overexpressing BLI-3 [13,35] was sufficient to increase the lifespan of C. elegans either on alive or heat-killed OP50 E. coli food source. In all three circumstances, the increased lifespan was completely dependent on BLI-3-generated ROS during adulthood and on SKN-1 [13,35].…”

Section: Bli-3-generated Ros Redox Signaling To Skn-1 To Promote Longmentioning

confidence: 99%

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Redox Signaling of NADPH Oxidases Regulates Oxidative Stress Responses, Immunity, and Aging

Ewald¹

2018

Preprint

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An accumulating body of evidence suggests that physiological reactive oxygen species (ROS) generated by NADPH oxidases act as a redox signal to re-establish homeostasis, a capacity that progressively declines during aging, but is maintained in long-lived animals to promote healthy aging. In the model organism Caenorhabditis elegans, ROS generated by dual oxidases (Duox) are important for extracellular matrix integrity, pathogen defense, oxidative stress resistance, and longevity. The Duox enzymatic activity is tightly regulated and under cellular control. Developmental molting cycles, pathogen infections, toxins, mitochondrial-derived ROS, drugs, and small GTPases (RHO-1) can activate Duox (BLI-3) to generate ROS, whereas NADPH oxidase inhibitors and negative regulators, such as MEMO-1, can inhibit Duox to generate ROS. Three mechanisms-of-action have been discovered for the Duox/BLI-3-generated ROS: 1) enzymatic activity to catalyze cross-linking of free tyrosine ethyl ester in collagen bundles to stabilize extracellular matrices, 2) high ROS bursts/levels to kill pathogens, and 3) Redox signaling activating downstream kinase cascades to transcription factors orchestrating oxidative stress- and immunity responses to re-establish homeostasis. Although Duox function at the cell surface is well established, recent genetic and biochemical data also suggests a novel role for Duoxs at the endoplasmic reticulum membrane to control redox signaling. Evidence underlying these mechanisms initiated by ROS from NADPH oxidases and their relevance for human aging are discussed in this review. Appropriately controlling NADPH oxidase activity for local and physiological redox signaling to maintain cellular homeostasis might be a therapeutic strategy to promote healthy aging.

show abstract

Lifespan extension by peroxidase and dual oxidase-mediated ROS signaling through pyrroloquinoline quinone in C. elegans

Cited by 35 publications

References 120 publications

Redox Signaling of NADPH Oxidases Regulates Oxidative Stress Responses, Immunity and Aging

Redox Signaling of NADPH Oxidases Regulates Oxidative Stress Responses, Immunity and Aging

ELT‐2 promotes O‐GlcNAc transferase OGT‐1 expression to modulate Caenorhabditis elegans lifespan

Redox Signaling of NADPH Oxidases Regulates Oxidative Stress Responses, Immunity, and Aging

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