Methionine oxidation activates pyruvate kinase M2 to promote pancreatic cancer metastasis

He, Dan; Feng, Huijin; Sundberg, Belen; Yang, Jun; Powers, Justin L.; Christian, Alec H.; Wilkinson, John E.; Monnin, Cian; Avizonis, Daina; Thomas, Craig J.; Friedman, Richard A.; Kluger, Michael D.; Hollingsworth, Michael A.; Grandgenett, Paul M.; Klute, Kelsey; Toste, F. Dean; Chang, Christopher J.; Chio, Iok In Christine

doi:10.1016/j.molcel.2022.06.005

Cited by 34 publications

(33 citation statements)

References 86 publications

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“…As methionine oxidation represents a reaction that can regulate protein function in vitro and in vivo (e.g. pyruvate kinase M2) (89,90), direct assessment of the role of CO2 on peroxide-dependent methionine oxidation (88, 91-94) becomes necessary 7 .…”

Section: Hydrogen Peroxide and Peroxymonocarbonatementioning

confidence: 99%

“…HCO 4 - also reacts faster with both free and protein-bound methionine ( e.g ., in α1-proteinase inhibitor) than H 2 O 2 , to yield the corresponding two-electron oxidation product methionine sulfoxide ( 88 ). As methionine oxidation represents a reaction that can regulate protein function in vitro and in vivo ( e.g ., pyruvate kinase M2) ( 89 , 90 ), direct assessment of the role of CO 2 on peroxide-dependent methionine oxidation ( 88 , 91 , 92 , 93 , 94 ) becomes necessary 7 .…”

Section: Chemical Aspects Of the Reaction Of Co 2 ...mentioning

confidence: 99%

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Interplay of carbon dioxide and peroxide metabolism in mammalian cells

Radí

2022

Journal of Biological Chemistry

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Section: Hydrogen Peroxide and Peroxymonocarbonatementioning

confidence: 99%

Section: Chemical Aspects Of the Reaction Of Co 2 ...mentioning

confidence: 99%

Interplay of carbon dioxide and peroxide metabolism in mammalian cells

Radí

2022

Journal of Biological Chemistry

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“…Assessing oxidative stress by looking downstream of ROS production (e.g., protein oxidative damage) largely overcomes these issues. Understanding the oxidative damage of proteins may also offer additional insight regarding protein function (e.g., inhibition [87] or activation [88] upon ROS-mediated oxidation). In this section, we present recent applications of small molecule probes for visualizing or identifying oxidized proteins.…”

Section: Mapping Protein Oxidative Damagementioning

confidence: 99%

“…The idea behind their approach was that oxidized methionine-containing proteins could be indirectly identified if the pool of probe-bound proteins between control (no ROS) and sample (with ROS) were compared (since ReACT can facilitate the MS-based identification of methionine-containing proteins). Application of this workflow recently demonstrated the power of this tool, as it revealed that pancreatic cancer metastasis is driven by methionine oxidation-mediated activation of pyruvate kinase M2 [88].…”

Section: Oxidized Methioninementioning

confidence: 99%

Oxidative Stress in Age-Related Neurodegenerative Diseases: An Overview of Recent Tools and Findings

2023

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Reactive oxygen species (ROS) have been described to induce a broad range of redox-dependent signaling reactions in physiological conditions. Nevertheless, an excessive accumulation of ROS leads to oxidative stress, which was traditionally considered as detrimental for cells and organisms, due to the oxidative damage they cause to biomolecules. During ageing, elevated ROS levels result in the accumulation of damaged proteins, which may exhibit altered enzymatic function or physical properties (e.g., aggregation propensity). Emerging evidence also highlights the relationship between oxidative stress and age-related pathologies, such as protein misfolding-based neurodegenerative diseases (e.g., Parkinson’s (PD), Alzheimer’s (AD) and Huntington’s (HD) diseases). In this review we aim to introduce the role of oxidative stress in physiology and pathology and then focus on the state-of-the-art techniques available to detect and quantify ROS and oxidized proteins in live cells and in vivo, providing a guide to those aiming to characterize the role of oxidative stress in ageing and neurodegenerative diseases. Lastly, we discuss recently published data on the role of oxidative stress in neurological disorders.

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“…A second interesting question is if mitochondrial metabolism is required for different tumor types that migrate to different metastatic destinations. Recent studies in other metastatic tumor types, including breast, pancreatic, and oral carcinomas suggest cancer cells upregulate and require respiration for metastatic progression [11][12][13]. This suggests the metabolic requirements for metastasis may be context dependent.…”

mentioning

confidence: 99%