Mitochondrial ferritin (FtMt) is a functional ferritin that localizes in the mitochondria. It is expressed in the testis, heart, brain, and cells with active respiratory activity. Its overexpression in cultured cells protected against oxidative damage and reduced cytosolic iron availability. However, no overt phenotype was previously described in mice with inactivation of the FtMt gene. Here, we used the doxorubicin model of cardiac injury in a novel strain of FtMt-null mice to investigate the antioxidant role of FtMt. These mice did not show any evident phenotype, but after acute treatment to doxorubicin, they showed enhanced mortality and altered heart morphology with fibril disorganization and severe mitochondrial damage. Signs of mitochondrial damage were present also in mock-treated FtMt−/− mice. The hearts of saline- and doxorubicintreated FtMt−/− mice had higher thiobarbituric acid reactive substance levels, heme oxygenase 1 expression, and protein oxidation, but did not differ from FtMt+/+ in the cardiac damage marker B-type natriuretic peptide (BNP), ATP levels, and apoptosis. However, the autophagy marker LC3 was activated. These results show that the absence of FtMt, which is highly expressed in the heart, increases the sensitivity of heart mitochondria to the toxicity of doxorubicin. This study represents the first in vivo evidence of the antioxidant role of FtMt.
|Titolo:||Mice lacking mitochondrial ferritin are more sensitive to doxorubicin-mediated cardiotoxicity|
GAMMELLA, ELENA (Primo)
CAIRO, GAETANO (Ultimo)
|Data di pubblicazione:||mag-2014|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Citazione:||Mice lacking mitochondrial ferritin are more sensitive to doxorubicin-mediated cardiotoxicity / E. Gammella, V. Diaz, S. Recalcati, P. Buratti, P. Santambrogio, V. Johannes, M. Gassmann, G. Cairo. ((Intervento presentato al convegno Cell Stress: Survival and Apoptosis tenutosi a Bertinoro nel 2014.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|