Mammalian mitochondria have the innate ability to import tRNAs by a mechanism distinct from protein import
Open accessAbstract
Mitochondrial genomes generally encode a minimal set of tRNAs necessary for protein synthesis. However, a number of eukaryotes import tRNAs from the cytoplasm into their mitochondria. For instance, Saccharomyces cerevisiae imports cytoplasmic tRNA(Gln) into the mitochondrion without any added protein factors. Here, we examine the existence of a similar active tRNA import system in mammalian mitochondria. We have used subcellular RNA fractions from rat liver and human cells to perform RT-PCR with oligonucleotide primers specific for nucleus-encoded tRNA(CUG)(Gln) and tRNA(UUG)(Gln) species, and we show that these tRNAs are present in rat and human mitochondria in vivo. Import of in vitro transcribed tRNAs, but not of heterologous RNAs, into isolated mitochondria also demonstrates that this process is tRNA-specific and does not require the addition of cytosolic factors. Although this in vitro system requires ATP, it is resistant to inhibitors of the mitochondrial electrochemical gradient, a key component of protein import. tRNA(Gln) import into mammalian mitochondria proceeds by a mechanism distinct from protein import. We also show that both tRNA(Gln) species and a bacterial pre-tRNA(Asp) can be imported in vitro into mitochondria isolated from myoclonic epilepsy with ragged-red fiber cells if provided with sufficient ATP (2 mM). This work suggests that tRNA import is more widespread than previously thought and may be a universal trait of mitochondria. Mutations in mitochondrial tRNA genes have been associated with human disease; the tRNA import system described here could possibly be exploited for the manipulation of defective mitochondria.
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Rubio et al. demonstrated import of cytosolic tRNA Gln(CUG) and tRNA Gln(UUG) in rat and human mitochondria in vivo by a mechanism distinct from protein import.
“Recently, Rubio et al. [243] have demonstrated the import of cytosolic tRNA Gln(CUG) and tRNA Gln(UUG) in rat and human mitochondria in vivo, by a mechanism distinct from that of protein import.”
From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [243]
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The Human Mitochondrial Transcriptome
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“[243] have demonstrated the import of cytosolic tRNA and tRNA in rat and humanmitochondria in vivo, by a mechanism distinct from that of protein import.”
BackgroundMitochondrial localization, import, and mitochondrial function of the androgen receptor
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“Both tRNACUGGln and tRNAUUGGln were also identified in mitochondria isolated from human and rat liver using sub-cellular fractionation and RT-PCR [62], providing in vivo relevance.”
BackgroundMethodInfluential
- Authors
- Rubio, M. A. T., Rinehart, J. J., Krett, B., Duvezin-Caubet, S., Reichert, A. S., Söll, D., & Alfonzo, J. D.
- Affiliations
- Yale University (US)
- The Ohio State University (US)
- Institute for Physiological Chemistry, Ludwig-Maximilians-University, Butenandtstrasse 5, 81377 Munich, Germany
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-07-08
- Volume
- 105
- Issue
- 27
- Pages
- 9186-9191
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2453747
- OpenAlex
- W2148427863
- Cited by
- 154
- References
- 38
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 11 · 2023: 8 · 2022: 7 · 2021: 5 · 2020: 11 · 2019: 11 · 2018: 5 · 2017: 9 · 2016: 7 · 2015: 12 · 2014: 4 · 2013: 7 · 2012: 14
- FWCI
- 4.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Deutsche Forschungsgemeinschaft (SFB 594)
- National Institute of General Medical Sciences (R01GM084065)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- tRNA import, mitochondrial tRNA, mammalian mitochondria, mitochondrial protein import, glutamine tRNA, mitochondrial genome, mitochondrial membrane potential, myoclonic epilepsy with ragged-red fibers, mitochondrial disease, pre-tRNA
- MeSH terms
- Adenosine Triphosphate, Animals, Base Sequence, Cell Nucleus, Cytosol, HeLa Cells, Humans, Mammals, Mitochondria, Mitochondria, Liver, Molecular Sequence Data, Nucleic Acid Conformation, RNA, Transfer, Gln, Solubility, MERRF Syndrome, Protein Transport, RNA Transport, Rats
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