Trends in Biochemical Sciences
ReviewRecent advances in tRNA mitochondrial import
Section snippets
tRNA transport into mitochondria
Mitochondria, organelles present in most eukaryotic cells, function in a variety of essential cellular processes including respiration, oxidative phosphorylation-mediated ATP production, cellular metabolism and apoptosis. They contain their own genome that encodes a limited number of macromolecules. Consequently, the majority of mitochondrial proteins are encoded in the nucleus and imported into the organelle (Box 1). In comparison to proteins, a low number of RNAs are imported into
Why must mitochondria import tRNAs?
In contrast to the human mitochondrial genome, which contains a minimal but complete set of tRNA genes, the number of tRNA-encoding genes in numerous mitochondrial genomes is insufficient for proper protein synthesis to occur. For example, protozoa such as Trypanosoma brucei and Leishmania tarentolae represent the most extreme situation because their mitochondrial genomes are completely devoid of tRNA genes. In the fungus Spizellomyces punctatus, only eight mitochondrially encoded tRNA genes
Divergent mechanisms for a convergent goal
As described, mitochondrial tRNA import is, in general, essential for mitochondrial protein synthesis; however, the ways to achieve this goal are clearly different. Elucidating the mechanisms for this process requires that several questions are answered (Box 2). What factors determine tRNA-import selectivity? How are tRNAs targeted from the nucleus to the mitochondrial surface? What protein factors constitute tRNA mitochondrial membrane import channels? Is the extent of tRNA import regulated?
An attractive tool for correcting disease-causing mitochondrial tRNA gene mutations
Mitochondrial DNA mutations are associated with many human diseases; more than half of these mutations are located within mitochondrial tRNA genes. The best characterized are MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERFF (myoclonic epilepsy and red ragged fibers) syndromes. The most prevalent point mutations associated with MELAS and MERFF syndrome are in mitochondrial trnL (Ala3243→Gly mutation) and trnK (Ala8344→Gly mutation), respectively
Concluding remarks and future perspectives
Several advances in the past several years have bolstered our understanding of how nuclear-encoded tRNAs are imported into the mitochondria of different organisms. It is remarkable to note that each organism recruits distinct housekeeping proteins to direct mitochondrial import 10, 27, 37, 45. Although the overall process of mitochondrial protein import is conserved 58, 59, it is tempting to speculate that divergent mechanisms for tRNA import have emerged to reach a convergent evolutionary
References (63)
Characterization of an RNase P activity from HeLa cell mitochondria. Comparison with the cytosol RNase P activity
J. Biol. Chem.
(1985)- et al.
Mitochondrial tRNA import: are there distinct mechanisms?
Trends Cell Biol.
(2000) Evidence for an adaptation mechanism of mitochondrial translation via tRNA import from the cytosol
Mol. Cell
(2007)RNA delivery into mitochondria
Adv. Drug Deliv. Rev.
(2001)Regulated tRNA import in Leishmania mitochondria
Biochim. Biophys. Acta
(1998)Sequence dependence of tRNAGly import into tobacco mitochondria
Biochimie
(2005)Identification and structural characterization of nucleus-encoded transfer RNAs imported into wheat mitochondria
J. Biol. Chem.
(2001)- et al.
The chloroplast derived trnW and trnM-e genes are not expressed in Arabidopsis mitochondria
Biochem. Biophys. Res. Commun.
(2001) The T-domain of cytosolic tRNAVal, an essential determinant for mitochondrial import
FEBS Lett.
(2005)Expression of Arabidopsis thaliana mitochondrial alanyl-tRNA synthetase is not sufficient to trigger mitochondrial import of tRNAAla in yeast
J. Biol. Chem.
(2000)
An intact protein translocating machinery is required for mitochondrial import of a yeast cytoplasmic tRNA
J. Mol. Biol.
Role of an RNA-binding protein in import of tRNA into Leishmania mitochondria
J. Biol. Chem.
An RNA-binding respiratory component mediates import of type II tRNAs into Leishmania mitochondria
J. Biol. Chem.
Detection of the mitochondrially encoded cytochrome c oxidase subunit I in the trypanosomatid protozoan Leishmania tarentolae. Evidence for translation of unedited mRNA in the kinetoplast
J. Biol. Chem.
The effect of RNA interference down-regulation of RNA editing 3′-terminal uridylyl transferase (TUTase) 1 on mitochondrial de novo protein synthesis and stability of respiratory complexes in Trypanosoma brucei
J. Biol. Chem.
Unusual polypeptide synthesis in the kinetoplast-mitochondria from Leishmania tarentolae. Identification of individual de novo translation products
J. Biol. Chem.
tRNA import into yeast mitochondria is regulated by the ubiquitin-proteasome system
FEBS Lett.
Strategies for treating disorders of the mitochondrial genome
Biochim. Biophys. Acta
Mitochondrial protein-import machinery: correlating structure with function
Trends Cell Biol.
The α-subunit of Leishmania F1 ATP synthase hydrolyzes ATP in presence of tRNA
J. Biol. Chem.
Mitochondrial genomes: anything goes
Trends Genet.
Evidence for the presence of 5S rRNA in mammalian mitochondria
Mol. Biol. Cell
Two distinct structural elements of 5S rRNA are needed for its import into human mitochondria
RNA
The RNase P associated with HeLa cell mitochondria contains an essential RNA component identical in sequence to that of the nuclear RNase P
Mol. Cell. Biol.
Import of nuclear DNA-encoded RNAs into mitochondria and mitochondrial translation
Cell Cycle
Coexistence of nuclear DNA-encoded tRNAVal(AAC) and mitochondrial DNA-encoded tRNAVal(UAC) in mitochondria of a liverwort Marchantia polymorpha
Nucleic Acids Res.
Saccharomyces cerevisiae imports the cytosolic pathway for Gln-tRNA synthesis into the mitochondrion
Genes Dev.
Elongation factor 1a mediates the specificity of mitochondrial tRNA import in T. brucei
EMBO J.
The anticodon is the signal sequence for mitochondrial import of glutamine tRNA in Tetrahymena
Genes Dev.
The D arm of tRNATyr is necessary and sufficient for import into Leishmania mitochondria in vitro
Nucleic Acids Res.
Mitochondrial RNA import in Leishmania tropica: aptamers homologous to multiple tRNA domains that interact cooperatively or antagonistically at the inner membrane
Mol. Cell. Biol.
Cited by (98)
Validation of Gene Therapy for Mutant Mitochondria by Delivering Mitochondrial RNA Using a MITO-Porter
2020, Molecular Therapy Nucleic AcidsThe single CCA-adding enzyme of T. Brucei has distinct functions in the cytosol and in mitochondria
2020, Journal of Biological ChemistryInterchangeable parts: The evolutionarily dynamic tRNA population in plant mitochondria
2020, MitochondrionCitation Excerpt :Such cases of ongoing and rapid mt-tRNA gene loss and presumed replacement by cytosolic import are noteworthy because they point to import specificity evolving remarkably fast. There are many longstanding and still unresolved questions on tRNA import mechanisms (Salinas et al., 2008), but what little is known about tRNA import in plants suggests that it is largely “complementary” (i.e., compensating for tRNA genes absent from the mitogenome rather than providing redundant tRNAs) and, at least in algae, “static” (i.e., tRNA pools were unaffected by manipulated mitogenome codon usage) (Salinas et al., 2012; Salinas et al., 2008; Vinogradova et al., 2009). Both of these observations provide evidence that tRNA import is a coevolved process based on historical tRNA requirements and mitogenome content.
Transfer RNA: From pioneering crystallographic studies to contemporary tRNA biology
2016, Archives of Biochemistry and BiophysicsCitation Excerpt :Then, two mitochondrial membrane proteins, Tb11.01.4590 and Tb09.v1.0420, together with Tim17 and Hsp70, are part of subsequent tRNA import machinery in the inner membrane showing that tRNA and protein import mechanisms share components [104]. Finally, in plants some TOM proteins are believed to act as tRNA receptors on the mitochondrial surface, while the voltage dependent anion channel (VDAC) may be the main translocation channel through the outer mitochondrial membrane [105]. In all of these systems tRNAs interact with β-barrel forming proteins such as VDAC, TOM40 or other components of the protein import machinery, presumably allowing them to cross mitochondrial membranes.