Regulation of the protein disulfide proteome by mitochondria in mammalian cells
Open accessAbstract
The majority of protein disulfides in cells is considered an important inert structural, rather than a dynamic regulatory, determinant of protein function. Here, we show that some disulfides in proteins also are regulated by cell redox status with functional consequences. We find that reactive oxygen species (ROS) produced by mitochondria are actively used by cells to facilitate cell-surface protein disulfide formation, as well as folding and transport, in mammalian cells. Inhibition of mitochondrial ROS production suppresses protein disulfide formation and induces reductive stress, leading to dysfunction and retention (possibly in the Golgi, in part) of a group of cell-surface disulfide-containing proteins. Sparsely cultured cells produce less ROS than confluent cells do, which leads to decreased disulfide formation and decreased activity of a subgroup of disulfide-containing cell-surface receptors. These data support the concept of two subproteomes comprising the disulfide proteome, a structural group and a redox-sensitive regulatory group, with the latter having direct functional consequences for the cell.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mitochondrial ROS play a large role in maintaining the oxidative homeostasis of the proteome.
“Mitochondrial ROS play a large role in maintaining the oxidative homeostasis of the proteome as inhibition of mitochondrial ROS production drastically decreases the total number of cellular protein disulfide bonds 48.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [48]
Inhibition of mitochondrial ROS production drastically decreases the total number of cellular protein disulfide bonds.
“inhibition of mitochondrial ROS production drastically decreases the total number of cellular protein disulfide bonds 48.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [48]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Epidermal Growth Factor (EGF)-induced Generation of Hydrogen Peroxide
Bae, Y. S., Kang, S. W., Seo, M. S., Baines, I., Tekle, E., Chock, P. B., & Rhee, S. G. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.1.217 · Cited by 1,208 · see citing works
Reversible Inactivation of the Tumor Suppressor PTEN by H2O2
Lee, S.-R., Yang, K., Kwon, J., Lee, C., Jeong, W., & Rhee, S. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111899200 · Cited by 1,061 · see citing works
Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo
Meng, T.-C., Fukada, T., & Tonks, N. K. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00445-8 · Cited by 1,040 · see citing works
Hydrogen Peroxide: A Key Messenger That Modulates Protein Phosphorylation Through Cysteine Oxidation
Rhee, S. G., Bae, Y. S., Lee, S.-R., & Kwon, J. (2000) · Science s STKE · doi:10.1126/stke.2000.53.pe1 · Cited by 646 · see citing works
Disulfide bonds as switches for protein function.
Hogg, P. (2003) · TIBS -Trends in Biochemical Sciences. Regular ed · doi:10.1016/s0968-0004(03)00057-4 · Cited by 581 · see citing works
Chaperone Activity with a Redox Switch
Jakob, U., Muse, W. B., Eser, M., & Bardwell, J. C. A. (1999) · Cell · doi:10.1016/s0092-8674(00)80547-4 · Cited by 513 · see citing works
The ERO1 Gene of Yeast Is Required for Oxidation of Protein Dithiols in the Endoplasmic Reticulum
Frand, A. R., & Kaiser, C. A. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80017-9 · Cited by 495 · see citing works
Biochemical Basis of Oxidative Protein Folding in the Endoplasmic Reticulum
Tu, B. P., Ho, S. C., Travers, K. J., & Weissman, J. S. (2000) · Science · doi:10.1126/science.290.5496.1571 · Cited by 448 · see citing works
Pollard, M. G., Travers, K. J., & Weissman, J. S. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80018-0 · Cited by 441 · see citing works
Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II
Choi, M. H., Lee, I. K., Kim, G. W., Kim, B. U., Han, Y.-H., Yu, D.-Y., Park, H. S., Kim, K. Y., Lee, J. S., Choi, C., et al. (2005) · Nature · doi:10.1038/nature03587 · Cited by 403 · see citing works
Oxidative Protein Folding Is Driven by the Electron Transport System
Bader, M. W., Muse, W. B., Ballou, D. P., Gassner, C., & Bardwell, J. C. A. (1999) · Cell · doi:10.1016/s0092-8674(00)81016-8 · Cited by 385 · see citing works
Bae, Y. S., Sung, J.-Y., Kim, O.-S., Kim, Y. J., Hur, K. C., Kazlauskas, A., & Rhee, S. G. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.14.10527 · Cited by 312 · see citing works
Lee, C., Lee, S. M., Mukhopadhyay, P., Kim, S. J., Lee, S. C., Ahn, W.-S., Yu, M., Storz, G., & Ryu, S. E. (2004) · Nature Structural & Molecular Biology · doi:10.1038/nsmb856 · Cited by 281 · see citing works
Pagani, M., Fabbri, M., Benedetti, C., Fassio, A., Pilati, S., Bulleid, N. J., Cabibbo, A., & Sitia, R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003061200 · Cited by 268 · see citing works
Manipulation of oxidative protein folding and PDI redox state in mammalian cells
Mezghrani, A., Fassio, A., Benham, A. M., Simmen, T., Braakman, I., & Sitia, R. (2001) · The EMBO Journal · doi:10.1093/emboj/20.22.6288 · Cited by 250 · see citing works
Protein Thiol Modifications Visualized In Vivo
Leichert, L., & Jakob, U. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020333 · Cited by 238 · see citing works
May, D., Itin, A., Gal, O., Kalinski, H., Feinstein, E., & Keshet, E. (2005) · Oncogene · doi:10.1038/sj.onc.1208325 · Cited by 167 · see citing works
<i>S</i> -nitrosoprotein formation and localization in endothelial cells
Yang, Y., & Loscalzo, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405989102 · Cited by 141 · see citing works
Self-citationThe cellular oxygen tension regulates expression of the endoplasmic oxidoreductase ERO1‐Lα
Gess, B., Hofbauer, K., Wenger, R. H., Lohaus, C., Meyer, H. E., & Kurtz, A. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03590.x · Cited by 132 · see citing works
Lodish, H. F., & Kong, N. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)80767-4 · Cited by 129 · see citing works
Frand, A. R., & Kaiser, C. A. (2000) · Molecular Biology of the Cell · doi:10.1091/mbc.11.9.2833 · Cited by 108 · see citing works
Chen, K., Albano, A., Ho, A., & Keaney, J. F. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304423200 · Cited by 95 · see citing works
Defining the plant disulfide proteome
Lee, K., Lee, J. J., Kim, Y., et al. (2004) · Electrophoresis · doi:10.1002/elps.200305677 · Cited by 79 · see citing works
Multiple Calcium Stores: Separate but Interacting
Lee, H. C. (2000) · Science s STKE · doi:10.1126/stke.2000.40.pe1 · Cited by 45 · see citing works
Zöllner, S. K., Aberle, S., Harvey, S. E., Polokoff, M. A., & Rubanyi, G. M. (2000) · Endothelium · doi:10.3109/10623320009165315 · Cited by 19 · see citing works
Extracellular cysteines define ectopeptidase (APN, CD13) expression and function
Firla, B., Arndt, M., Frank, K., et al. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00827-9 · Cited by 18 · see citing works
The dance of disulfide formation
Bardwell, J. C. A. (2004) · Nature Structural & Molecular Biology · doi:10.1038/nsmb0704-582 · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [14]Lodish HF, Kong N. J Biol Chem. 1993;268:20598–20605. [PubMed] [Google Scholar]
- [17]Bae YS, Kang SW, Seo MS, Baines IC, Tekle E, Chock PB, Rhee SG. J Biol Chem. 1997;272:217–221. [PubMed] [Google Scholar]
Cited by
Sorted by citations
Lubos, E., Loscalzo, J., & Handy, D. E. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3586 · Cited by 1,280 · see citing works
Self-citationMitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes
Hamanaka, R. B., & Chandel, N. S. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.04.002 · Cited by 1,011 · see citing works
Role of peroxisomes in ros/rns-metabolism: Implications for human disease
Fransen, M., Nordgren, M., Wang, B., & Apanasets, O. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.12.001 · Cited by 644 · see citing works
Redox regulation of mitochondrial function
Handy, D. E., & Loscalzo, J. (2012) · Antioxidants & Redox Signaling · doi:10.1089/ars.2011.4123 · Cited by 588 · see citing works
Self-citationSantos, C. X. C., Tanaka, L. Y., Wosniak, J., & Laurindo, F. R. M. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2625 · Cited by 572 · see citing works
Redox interplay between mitochondria and peroxisomes
Lismont, C., Nordgren, M., Van Veldhoven, P. P., & Fransen, M. (2015) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2015.00035 · Cited by 214 · see citing works
Handy, D. E., Lubos, E., Yang, Y., Galbraith, J. D., Kelly, N., Zhang, Y.-Y., Leopold, J. A., & Loscalzo, J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900392200 · Cited by 187 · see citing works
Self-citation
- Authors
- Yang, Y., Song, Y., & Loscalzo, J.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Loscalzo, Joseph
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-06-26
- Volume
- 104
- Issue
- 26
- Pages
- 10813-10817
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1904139
- OpenAlex
- W1988862712
- Cited by
- 129
- References
- 27
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 8 · 2016: 4 · 2015: 7 · 2014: 13 · 2013: 10 · 2012: 8
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Update notices
- correction (2009-08-25)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education of the People's Republic of China
- National Institutes of Health (n01hv28178-12-0-0, HL55993, HL 58976, HL 61795, HV28178)
- National Heart, Lung, and Blood Institute (HL61795, HV-28178, HL58976, R01HL058976, P01HL081587, P01HL81587, N01-HV-028178, R01HL061795, P50HL055993, R37HL061795)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Keywords
- mitochondria, reactive oxygen species, redox regulation, cell surface proteins, protein folding, protein trafficking, reductive stress, Golgi retention, cell surface receptors, cell confluence, disulfide bond formation
- MeSH terms
- Animals, Cells, Disulfides, Mammals, Membrane Proteins, Mitochondria, Oxidation-Reduction, Reactive Oxygen Species, Oxidative Stress, Proteome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
