Publication: Novel role of 4-hydroxy-2-nonenal in AIFm2-mediated mitochondrial stress signaling
Issued Date
2016-02-01
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ISSN
18734596
08915849
08915849
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2-s2.0-84951091711
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Mahidol University
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SCOPUS
Bibliographic Citation
Free Radical Biology and Medicine. Vol.91, (2016), 68-80
Suggested Citation
Sumitra Miriyala, Chadinee Thippakorn, Luksana Chaiswing, Yong Xu, Teresa Noel, Artak Tovmasyan, Ines Batinic-Haberle, Craig W. Vander Kooi, Wang Chi, Ahmed Abdel Latif, Manikandan Panchatcharam, Virapong Prachayasittikul, D. Allan Butterfield, Mary Vore, Jeffrey Moscow, Daret K.St Clair Novel role of 4-hydroxy-2-nonenal in AIFm2-mediated mitochondrial stress signaling. Free Radical Biology and Medicine. Vol.91, (2016), 68-80. doi:10.1016/j.freeradbiomed.2015.12.002 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/43115
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Title
Novel role of 4-hydroxy-2-nonenal in AIFm2-mediated mitochondrial stress signaling
Abstract
© 2015 Elsevier Inc. All rights reserved. Cardiovascular complications are major side effects of many anticancer drugs. Accumulated evidence indicates that oxidative stress in mitochondria plays an important role in cardiac injury, but how mitochondrial redox mechanisms are involved in cardiac dysfunction remains unclear. Here, we demonstrate that 4-hydroxy-2-nonenal (HNE) activates the translocation of the mitochondrial apoptosis inducing factor (AIFm2) and facilitates apoptosis in heart tissue of mice and humans. Doxorubicin treatments significantly enhance cardiac levels of HNE and AIFm2. HNE adduction of AIFm2 inactivates the NADH oxidoreductase activity of AIFm2 and facilitates its translocation from mitochondria. His 174 on AIFm2 is the critical target of HNE adduction that triggers this functional switch. HNE adduction and translocation of AIFm2 from mitochondria upon Doxorubicin treatment are attenuated by superoxide dismutase mimetics. These results identify a previously unrecognized role of HNE with important consequences for mitochondrial stress signaling, heart failure, and the side effects of cancer therapy.