A pool of extramitochondrial frataxin that promotes cell survival.
Frataxin is a mitochondrial protein involved in iron metabolism. Defective expression of frataxin causes Friedreich ataxia (FA), an inherited degenerative syndrome characterized by ataxia, cardiomyopathy, and high incidence of diabetes. Here we report that frataxin-deficient cells are more prone to undergo stress-induced mitochondrial damage and apoptosis, while the overexpression of frataxin confers protection to a variety of cell types. Moreover, we reveal the existence of an extramitochondrial pool of frataxin, which can efficiently prevent mitochondrial damage and apoptosis in different cellular systems. Remarkably, extramitochondrial frataxin can fully replace mitochondrial frataxin in promoting survival of FA cells.
Condò
Ivano
I
Laboratory of Signal Transduction, Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, via Montpellier 1, 00133 Rome, Italy.
Ventura
Natascia
N
Malisan
Florence
F
Tomassini
Barbara
B
Testi
Roberto
R
D000975:Antioxidants / Q000737:chemistry; D017209:Apoptosis; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D045304:Cytochromes c / Q000378:metabolism; D005621:Friedreich Ataxia / Q000473:pathology; D006367:HeLa Cells; D006801:Humans; D033862:Iron-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D019169:Jurkat Cells; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D000096923:Frataxin
D000975:Antioxidants; D045304:Cytochromes c; D033862:Iron-Binding Proteins; D017382:Reactive Oxygen Species; D000096923:Frataxin