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J Cell Sci. 2019 Oct 1;132(19). pii: jcs223891. doi: 10.1242/jcs.223891.

Mitochondrial Alkbh1 localizes to mtRNA granules and its knockdown induces the mitochondrial UPR in humans and C. elegans.

Author information

1
Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
2
Department of Biology II, Center for Integrated Protein Science Munich, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany.
3
Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia.
4
Institute of Toxicology and Environmental Hygiene, School of Medicine, Technical University Munich, 80802 Munich, Germany.
5
Assay Development and Screening Platform, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
6
Institute of Pathology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany.
7
Center for Integrated Protein Science at the Department of Chemistry, Chair of Biochemistry, Technical University of Munich, Lichtenbergstrasse 4, 85748 Garching, Germany.
8
Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München-German Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany alexander.wolf@helmholtz-muenchen.de.

Abstract

The Fe(II) and 2-oxoglutarate-dependent oxygenase Alkb homologue 1 (Alkbh1) has been shown to act on a wide range of substrates, like DNA, tRNA and histones. Thereby different enzymatic activities have been identified including, among others, demethylation of N 3-methylcytosine (m3C) in RNA- and single-stranded DNA oligonucleotides, demethylation of N 1-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 visualizing localization 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 Caenorhabditis elegans, where the mitochondrial role of Alkbh1 seems to be conserved. Alkbh1 knockdown, but not Alkbh7 knockdown, triggers the mitochondrial unfolded protein response (UPRmt) in C. elegans.

KEYWORDS:

Fe(II) and 2-oxoglutarate dependent oxygenase; Jumonji-domain-containing enzyme; Mitochondrial structure; Mitochondrial unfolded protein response; RNA granules; RNA modifications

PMID:
31434717
DOI:
10.1242/jcs.223891

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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