Redox Signaling from and to Peroxisomes: Progress, Challenges, and Prospects

Fransen, Marc; Lismont, Celien

doi:10.1089/ars.2018.7515

Cited by 56 publications

(44 citation statements)

References 188 publications

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“…In addition, the functional correlation between disease pathogenesis and alterations in peroxisome physiology has to be deciphered. Other rapidly developing research areas include the role of peroxisomes in cellular redox balance and redox signalling (Fransen and Lismont 2018 ) and in antiviral signalling and defence (Wong et al 2018 ). Peroxisomes are still among the more mysterious subcellular compartments in eukaryotic cells, but there is no doubt that they are “on the rise” and poised to reveal more surprises in the near future.…”

Section: Discussionmentioning

confidence: 99%

The peroxisome: an update on mysteries 2.0

Islinger

Voelkl

Fahimi

et al. 2018

Histochem Cell Biol

244

227

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Peroxisomes are key metabolic organelles, which contribute to cellular lipid metabolism, e.g. the β-oxidation of fatty acids and the synthesis of myelin sheath lipids, as well as cellular redox balance. Peroxisomal dysfunction has been linked to severe metabolic disorders in man, but peroxisomes are now also recognized as protective organelles with a wider significance in human health and potential impact on a large number of globally important human diseases such as neurodegeneration, obesity, cancer, and age-related disorders. Therefore, the interest in peroxisomes and their physiological functions has significantly increased in recent years. In this review, we intend to highlight recent discoveries, advancements and trends in peroxisome research, and present an update as well as a continuation of two former review articles addressing the unsolved mysteries of this astonishing organelle. We summarize novel findings on the biological functions of peroxisomes, their biogenesis, formation, membrane dynamics and division, as well as on peroxisome–organelle contacts and cooperation. Furthermore, novel peroxisomal proteins and machineries at the peroxisomal membrane are discussed. Finally, we address recent findings on the role of peroxisomes in the brain, in neurological disorders, and in the development of cancer.

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Section: Discussionmentioning

confidence: 99%

The peroxisome: an update on mysteries 2.0

Islinger

Voelkl

Fahimi

et al. 2018

Histochem Cell Biol

244

227

View full text Add to dashboard Cite

show abstract

“…In addition, peroxisomes also contain nitric oxide synthase (NOS2), which generates NO. To counterbalance ROS production, peroxisomes possess several antioxidant enzymes, such as catalase (CAT), superoxide dismutase 1 (SOD1), peroxiredoxin 5 (PRDX5), glutathione S-transferase kappa 1 (GSTK1) and glutathione peroxidase (GPx) [144,145]. The role of peroxisomes within the cellular redox landscape is not fully understood, but it has been suggested that their function as a source or sink for H 2 O 2 is tissue-specific [144].…”

Section: Peroxisomesmentioning

confidence: 99%

“…To counterbalance ROS production, peroxisomes possess several antioxidant enzymes, such as catalase (CAT), superoxide dismutase 1 (SOD1), peroxiredoxin 5 (PRDX5), glutathione S-transferase kappa 1 (GSTK1) and glutathione peroxidase (GPx) [144,145]. The role of peroxisomes within the cellular redox landscape is not fully understood, but it has been suggested that their function as a source or sink for H 2 O 2 is tissue-specific [144]. Nevertheless, peroxisomal function and redox metabolism are important for metabolic reprogramming and are crucially involved in cancer development [146].…”

Section: Peroxisomesmentioning

confidence: 99%

Targeting the Redox Landscape in Cancer Therapy

Narayanan

Özcelik

2020

Cancers

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Reactive oxygen species (ROS) are produced predominantly by the mitochondrial electron transport chain and by NADPH oxidases in peroxisomes and in the endoplasmic reticulum. The antioxidative defense counters overproduction of ROS with detoxifying enzymes and molecular scavengers, for instance, superoxide dismutase and glutathione, in order to restore redox homeostasis. Mutations in the redox landscape can induce carcinogenesis, whereas increased ROS production can perpetuate cancer development. Moreover, cancer cells can increase production of antioxidants, leading to resistance against chemo- or radiotherapy. Research has been developing pharmaceuticals to target the redox landscape in cancer. For instance, inhibition of key players in the redox landscape aims to modulate ROS production in order to prevent tumor development or to sensitize cancer cells in radiotherapy. Besides the redox landscape of a single cell, alternative strategies take aim at the multi-cellular level. Extracellular vesicles, such as exosomes, are crucial for the development of the hypoxic tumor microenvironment, and hence are explored as target and as drug delivery systems in cancer therapy. This review summarizes the current pharmaceutical and experimental interventions of the cancer redox landscape.

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“…For instance, in mammals, there are only about 50 different proteins in the organelle matrix . These proteins are mainly enzymes participating in metabolic pathways such as synthesis of plasmalogens and bile acids, β‐oxidation of very long chain fatty acids, and detoxification of glyoxylate and ROS .…”

Section: Peroxisomal Targeting Signals Their Receptors and The Impomentioning

confidence: 99%

The intrinsically disordered nature of the peroxisomal protein translocation machinery

et al. 2018

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Despite having a membrane that is impermeable to all but the smallest of metabolites, peroxisomes acquire their newly synthesized (cytosolic) matrix proteins in an already folded conformation. In some cases, even oligomeric proteins have been reported to translocate the organelle membrane. The protein sorting machinery that accomplishes this feat must be rather flexible and, unsurprisingly, several of its key components have large intrinsically disordered domains. Here, we provide an overview on these domains and their interactions trying to infer their functional roles in this protein sorting pathway.

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Redox Signaling from and to Peroxisomes: Progress, Challenges, and Prospects

Abstract: As the precise molecular mechanisms underlying many of these associations are still poorly understood, a key focus for future research should be the identification of primary targets for peroxisome-derived HO.

Cited by 56 publications

References 188 publications

The peroxisome: an update on mysteries 2.0

The peroxisome: an update on mysteries 2.0

Targeting the Redox Landscape in Cancer Therapy

The intrinsically disordered nature of the peroxisomal protein translocation machinery

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