MTPA: a crustacean metallothionein that affects hepatopancreatic mitochondrial functions
Eduardo Moltó1, Elena Bonzón-Kulichenko, Nilda Gallardo
1Biochemistry Section, Faculty of Chemistry, Regional Centre for Biomedical Research (CRIB), University of Castilla-La Mancha, Camilo José Cela, 10, 13071 Ciudad Real, Spain.
Abstract:
Metallothioneins are cysteine-rich proteins, with a high capacity to bind metallic ions, and for which a precise biological role has not been established. Here we investigated the effects of MTPA, a metallothionein from the lobster Panulirus argus, on mitochondrial oxygen consumption and ROS production. An HPLC-RP-ESI-MS analysis of recombinant MTPA showed that despite its extra Cys, MTPA binds 6 Zn2+ per molecule akin to other crustacean metallothioneins with 18 Cys. The extra Cys is not involved in zinc binding, since its side-chain would be oriented to the outside of the molecule according to a preliminary model of the tridimensional structure of MTPA. MTPA-Zn2+(6) is imported into the hepatopancreatic mitochondria intermembrane space and inhibits mitochondrial oxygen consumption, increasing thereby ROS production. Nevertheless, the stimulation of ROS production by MT-bound Zn2+ is weaker compared to equivalent amounts of free Zn2+, suggesting that MTPA protects against oxidative stress. This constitutes the first report on metallothioneins effects on mitochondrial function in invertebrates and agrees with the results described for mammals, suggesting a connection between metallothioneins and energy metabolism.
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