Measurement of H2O2 within Living Drosophila during Aging Using a Ratiometric Mass Spectrometry Probe Targeted to the Mitochondrial Matrix
Open accessAbstract
Hydrogen peroxide (H(2)O(2)) is central to mitochondrial oxidative damage and redox signaling, but its roles are poorly understood due to the difficulty of measuring mitochondrial H(2)O(2) in vivo. Here we report a ratiometric mass spectrometry probe approach to assess mitochondrial matrix H(2)O(2) levels in vivo. The probe, MitoB, comprises a triphenylphosphonium (TPP) cation driving its accumulation within mitochondria, conjugated to an arylboronic acid that reacts with H(2)O(2) to form a phenol, MitoP. Quantifying the MitoP/MitoB ratio by liquid chromatography-tandem mass spectrometry enabled measurement of a weighted average of mitochondrial H(2)O(2) that predominantly reports on thoracic muscle mitochondria within living flies. There was an increase in mitochondrial H(2)O(2) with age in flies, which was not coordinately altered by interventions that modulated life span. Our findings provide approaches to investigate mitochondrial ROS in vivo and suggest that while an increase in overall mitochondrial H(2)O(2) correlates with aging, it may not be causative.
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MitoB is a mitochondria-targeted mass spectrometric hydrogen peroxide probe that allows quantification of mitochondrial hydrogen peroxide in vivo.
“We recently developed MitoB, a mitochondria-targeted mass spectrometric hydrogen peroxide probe, which allows for quantification of mitochondrial hydrogen peroxide in vivo20.”
From Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I (2013) · cites this paper as [20]
Mitochondrial hydrogen peroxide flux in vivo was measured using the MitoB mass spectrometric probe as previously described.
“We measured mitochondrial hydrogen peroxide in vivo using the MitoB mass spectro-metric probe as described previously20.”
From Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I (2013) · cites this paper as [20]
Tissue samples were spiked with deuterated internal standards for quantification of MitoB and MitoP.
“For analysis, we spiked the tissues with deuterated internal standards, extracted the MitoB and its product MitoP from the reaction with hydrogen peroxide and determined the amounts of MitoB and MitoP present in the tissue by liquid chromatography and tandem mass spectrometry as described previously20.”
From Cardioprotection by S-nitrosation of a cysteine switch on mitochondrial complex I (2013) · cites this paper as [20]
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- Authors
- Cochemé, H. M., Quin, C., McQuaker, S. J., Cabreiro, F., Logan, A., Prime, T. A., Abakumova, I., Patel, J. V., Fearnley, I. M., James, A. M., Porteous, C. M., Smith, R. A. J., Saeed, S., Carré, J. E., Singer, M., Gems, D., Hartley, R. C., Partridge, L., & Murphy, M. P.
- Affiliations
- University College London (GB)
- University of Glasgow (GB)
- MRC Mitochondrial Biology Unit (GB)
- University of Otago (NZ)
- Corresponding author
- Murphy, Michael P.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 13
- Issue
- 3
- Pages
- 340-350
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4413513
- OpenAlex
- W2026738371
- Cited by
- 313
- References
- 30
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 11 · 2023: 12 · 2022: 15 · 2021: 28 · 2020: 21 · 2019: 22 · 2018: 18 · 2017: 24 · 2016: 21 · 2015: 28 · 2014: 13 · 2013: 31 · 2012: 27
- FWCI
- 11.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Wellcome Trust
- National Institute for Health and Care Research
- Swansea University
- University College London Hospitals NHS Foundation Trust
- Engineering and Physical Sciences Research Council
- Biotechnology and Biological Sciences Research Council (BB/D020786/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- hydrogen peroxide, mitochondrial matrix, mitochondrial reactive oxygen species, aging, Drosophila, arylboronic acids, triphenylphosphonium, thoracic muscles, lifespan
- MeSH terms
- Aging, Animals, Chromatography, High Pressure Liquid, Drosophila, Hydrogen Peroxide, Mitochondria, Organophosphorus Compounds, Phenols, Tandem Mass Spectrometry
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