Cited by 665Redox biology and oxidative stressCell death mechanisms and regulationGlutathione Transferases and Polymorphisms

The diverse functions of GAPDH: Views from different subcellular compartments

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Tristan, Carlos, Shahani, Neelam, Sedlak, Thomas W., Sawa, Akira·2011·Cellular Signalling

Abstract

Multiple roles for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) have been recently appreciated. In addition to the cytoplasm where the majority of GAPDH is located under the basal condition, GAPDH is also found in the particulate fractions, such as the nucleus, the mitochondria, and the small vesicular fractions. When cells are exposed to various stressors, dynamic subcellular re-distribution of GAPDH occurs. Here we review these multifunctional properties of GAPDH, especially linking them to its oligomerization, posttranslational modification, and subcellular localization. This includes mechanistic descriptions of how S-nitrosylation of GAPDH under oxidative stress may lead to cell death/dysfunction via nuclear translocation of GAPDH, which is counteracted by a cytosolic GOSPEL. GAPDH is also involved in various diseases, especially neurodegenerative disorders and cancers. Therapeutic strategies to these conditions based on molecular understanding of GAPDH are discussed.

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Crossref · 10.1016/j.cellsig.2010.08.003

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  • Redox changes may also affect posttranslational modifications of GAPDH, altering its binding to mRNA, metabolites, as well as its localization within the cell.

    “Redox changes may also affect posttranslational modifications of GAPDH, altering its binding to mRNA, metabolites, as well as its localization within the cell (113, 114).”

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  1. [24]Brune B Lapetina EG Genet Eng (N Y) 17 1995 149 7540026
  2. [45]Kusner LL Sarthy VP Mohr S Invest Ophthalmol Vis Sci 45 2004 1553 15111614

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Authors
Tristan, C., Shahani, N., Sedlak, T. W., & Sawa, A.
Affiliations
Johns Hopkins University (US)
Corresponding author
Sawa, Akira
Venue
Cellular Signalling
Publisher
Elsevier BV
Published
2011-02
Volume
23
Issue
2
Pages
317-323
ISSN
0898-6568 (ISSN-L)
OpenAlex
W2139503567
Cited by
663
References
86
Citations by year
2026: 43 · 2025: 49 · 2024: 34 · 2023: 42 · 2022: 47 · 2021: 67 · 2020: 53 · 2019: 37 · 2018: 38 · 2017: 49 · 2016: 40 · 2015: 37 · 2014: 37 · 2013: 37 · 2012: 37
FWCI
2.52
Type
journal article
Language
en
Open access
Locations
  • Cellular Signalling (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • USPHS (MH-084018, MH-069853, MH-085226, MH-088753)
  • Stanley
  • CHDI
  • HighQ
  • RUSK
  • NARSAD
  • NINDS
  • S-R
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Keywords
glyceraldehyde-3-phosphate dehydrogenase, nuclear translocation, S-nitrosylation, oxidative stress, post-translational modification, protein oligomerization, Gospels, neurodegenerative diseases, cancer, cell death
MeSH terms
Animals, Cell Nucleus, Cytoplasm, Cytoskeleton, Glyceraldehyde-3-Phosphate Dehydrogenases, Humans, Mitochondria, Vesicular Transport Proteins

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