The Fe(II) and 2-oxoglutarate dependent oxygenase Alkb homolog 1 (Alkbh1) has been shown to act on a wide range of substrates, like DNA, tRNA or histones. Thereby different enzymatic activities have been identified including, amongst others demethylation of N3-methylcytosine (m3C) in RNA- and single-stranded DNA-oligonucleotides, demethylation of N1-methyladenosine (m1A) in tRNA or formation of 5-formyl cytosine (f5C) in tRNA. In accordance with the different substrates Alkbh1 has also been proposed to reside in distinct cellular compartments in human and mouse cells, including the nucleus, cytoplasm and mitochondria. Here we describe further evidence for a role of human Alkbh1 in regulation of mitochondrial protein biogenesis, including localisation of Alkbh1 into mitochondrial RNA granules with super-resolution 3D SIM microscopy. Electron microscopy and high-resolution respirometry analyses revealed an impact of Alkbh1 level on mitochondrial respiration, but not on mitochondrial structure. Downregulation of Alkbh1 impacts cell growth in Hela cells and delays development in C. elegans, where the mitochondrial role of Alkbh1 seems to be conserved. Alkbh1 knockdown, but not Alkbh7 knockdown, triggers mitochondrial unfolded protein response (UPRmt) in C. elegans.
Mitochondrial Alkbh1 localises to mtRNA granules and its knockdown induces mitochondrial UPR in humans and C. elegans
present address: Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Finland
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Anita Wagner, Olga Hofmeister, Stephane G. Rolland, Andreas Maiser, Koit Aasumets, Sabine Schmitt, Kenji Schorpp, Annette Feuchtinger, Kamyar Hadian, Sabine Schneider, Hans Zischka, Heinrich Leonhardt, Barbara Conradt, Joachim M. Gerhold, Alexander Wolf; Mitochondrial Alkbh1 localises to mtRNA granules and its knockdown induces mitochondrial UPR in humans and C. elegans. J Cell Sci 2019; jcs.223891. doi: https://doi.org/10.1242/jcs.223891
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