AI Article Synopsis
- MTH1 is an enzyme that helps maintain the quality of nucleotide pools by breaking down oxidized nucleotides, crucial for preventing errors in DNA during oxidative stress.
- The study found that MTH1 is expressed in platelets and its absence leads to issues with blood clotting (hemostasis) and increased risk of thrombosis.
- MTH1 deficiency also causes reduced platelet function and increased mitochondrial DNA damage, hinting that targeting MTH1 could be a new way to treat thrombotic diseases.
Article Abstract
Human MutT Homolog 1 (MTH1) is a nucleotide pool sanitization enzyme that hydrolyzes oxidized nucleotides to prevent their mis-incorporation into DNA under oxidative stress. Expression and functional roles of MTH1 in platelets are not known. Here, we show MTH1 expression in platelets and its deficiency impairs hemostasis and arterial/venous thrombosis in vivo. MTH1 deficiency reduced platelet aggregation, phosphatidylserine exposure and calcium mobilization induced by thrombin but not by collagen-related peptide (CRP) along with decreased mitochondrial ATP production. Thrombin but not CRP induced Ca-dependent mitochondria reactive oxygen species generation. Mechanistically, MTH1 deficiency caused mitochondrial DNA oxidative damage and reduced the expression of cytochrome c oxidase 1. Furthermore, MTH1 exerts a similar role in human platelet function. Our study suggests that MTH1 exerts a protective function against oxidative stress in platelets and indicates that MTH1 could be a potential therapeutic target for the prevention of thrombotic diseases.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415391 | PMC |
| http://dx.doi.org/10.1038/s41467-023-40600-7 | DOI Listing |
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