Characterization of the mitochondrial isoform of FASTK

Abstract

The Fas‐Activated Serine/Threonine kinase (FASTK) is a protein that regulates alternative splicing in the nucleus (Simarro et al., 2007). This protein is also present in the cytosol where it is associated to stress granules and processing bodies (Kedersha et al., 2005). FASTK is the founding member of the FASTKD family, which contains five other proteins (1–5). These proteins localize to mitochondria (Simarro et al., 2009) and recently FASTKD2 has been reported to regulate cytochrome c oxidase activity (Ghezzi et al., 2008), whereas FASTKD3 is required for mitochondrial respiration. Importantly, FASTKD2 has been identified to be mutated in a case of mitochondrial encephalomyopathy.We have characterized the two different isoforms of FASTK and we have found that the isoform 1 of the protein contains an internal and atypical mitochondrial targeting signal. This isoform is in the mitochondrial inner membrane with its domains exposed to the matrix. Interestingly, we also found that in mitochondria FASTK is not equally distributed but is rather concentrated in particular foci within mitochondria. We are now investigating the function of FASTK in mitochondria, as well as of the FASTKDs.