Regulation of Calcium Fluxes by GPX8, a Type-II Transmembrane Peroxidase Enriched at the Mitochondria-Associated Endoplasmic Reticulum Membrane

GPX8(一种富含线粒体相关内质网膜的 II 型跨膜过氧化物酶)对钙通量的调节

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作者:Edgar Djaha Yoboue, Alessandro Rimessi, Tiziana Anelli, Paolo Pinton, Roberto Sitia

Aims

Investigating whether and how GPX8 impacts Ca2+ homeostasis and signaling.

Conclusion

The notion that the TMD of GPX8, in addition to its enzymatic activity, is essential for regulating Ca2+ dynamics reveals a novel level of integration between redox-related proteins and Ca2+ signaling/homeostasis. Antioxid. Redox Signal. 27, 583-595.

Results

We show that GPX8 is enriched in mitochondria-associated membranes and regulates Ca2+ storage and fluxes. Its levels correlate with [Ca2+]ER, and cytosolic and mitochondrial Ca2+ fluxes. GPX7, which lacks a TMD, does not share these properties. Deleting or replacing the GPX8 TMD with an unrelated N-terminal membrane integration sequence abolishes all effects on Ca2+ fluxes, whereas appending the GPX8 TMD to GPX7 transfers the Ca2+-regulating properties. Innovation and

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