Phospholipid hydroperoxide glutathione peroxidase
GeneName
GPX4
Summary
GPX4, also known as glutathione peroxidase 4, PHGPx, or phospholipid hydroperoxide glutathione peroxidase, is a 22 kDa enzyme that plays a vital role in protecting cells from oxidative damage. It is primarily expressed in the cytosol, mitochondria, and nucleus, and is involved in the detoxification of lipid hydroperoxides and the regulation of reactive oxygen species. GPX4 exhibits glutathione peroxidase activity and is essential for processes such as apoptosis, chromatin organisation, and response to oxidative stress. It is also implicated in the negative regulation of ferroptosis, a form of regulated cell death associated with iron and lipid peroxidation.
Importance
GPX4 is relevant to: - The study of oxidative stress and its implications in various diseases, including cancer and neurodegenerative disorders - Understanding ferroptosis and its role in cell death, which has potential therapeutic applications in cancer treatment - Research into lipid metabolism and its effects on cellular health and disease - The development of strategies to enhance cellular resilience against oxidative damage, which may have implications in ageing and chronic diseases
Top Products
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Abcam Product Citation Summary
The data indicates a significant focus on the role of GPX4 in various contexts related to ferroptosis, oxidative stress, and cellular injury across multiple species, particularly in mouse and rat models. The studies employ Western blotting as the primary application to investigate GPX4 expression in different tissues, including the brain, liver, and intestines, highlighting its importance in neuroprotection and cellular defence mechanisms.
Abcam Product Citation Table
Function
Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (By similarity). Can also reduce cholesterol hydroperoxide and thymine hydroperoxide (By similarity). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (By similarity). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species (PubMed:24439385). The presence of selenocysteine (Sec) versus Cys at the active site is essential for life: it provides resistance to overoxidation and prevents cells against ferroptosis (By similarity). The presence of Sec at the active site is also essential for the survival of a specific type of parvalbumin-positive interneurons, thereby preventing against fatal epileptic seizures (By similarity). May be required to protect cells from the toxicity of ingested lipid hydroperoxides (By similarity). Required for normal sperm development and male fertility (By similarity). Essential for maturation and survival of photoreceptor cells (By similarity). Plays a role in a primary T-cell response to viral and parasitic infection by protecting T-cells from ferroptosis and by supporting T-cell expansion (By similarity). Plays a role of glutathione peroxidase in platelets in the arachidonic acid metabolism (PubMed:11115402). Reduces hydroperoxy ester lipids formed by a 15-lipoxygenase that may play a role as down-regulator of the cellular 15-lipoxygenase pathway (By similarity). Can reduce fatty acid-derived hydroperoxides (PubMed:11115402, PubMed:36608588). Can also reduce small soluble hydroperoxides such as H2O2, cumene hydroperoxide and tert-butyl hydroperoxide (PubMed:17630701, PubMed:36608588).
Involvement in disease
Spondylometaphyseal dysplasia, Sedaghatian type
SMDS
A form of spondylometaphyseal dysplasia, a group of short stature disorders distinguished by abnormalities in the vertebrae and the metaphyses of the tubular bones. SMDS is a neonatal lethal form characterized by severe metaphyseal chondrodysplasia with mild limb shortening, platyspondyly, cardiac conduction defects, and central nervous system abnormalities.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the glutathione peroxidase family.
Tissue Specificity
Present primarily in testis. Expressed in platelets (at protein level) (PubMed:11115402).
Cellular localization
- Isoform Mitochondrial
- Mitochondrion
- Isoform Cytoplasmic
- Cytoplasm
Alternative names
Phospholipid hydroperoxide glutathione peroxidase GPX4, PHGPx, Glutathione peroxidase 4, GPx-4, GSHPx-4, GPX4