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Recent advances in tRNA mitochondrial import

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In many eukaryotes, tRNA import from the cytosol into mitochondria is essential for mitochondrial biogenesis and, consequently, for cell viability. Recent work has begun to unravel the molecular mechanisms involved in tRNA transport in yeast, trypanosomatids and plants. The mechanisms of tRNA targeting to, and translocation through, the double mitochondrial membrane in addition to how selectivity and regulation of these processes are achieved are the main questions that have been addressed. The characterization of both direct and co-import mechanisms involving distinct protein-import factors is in agreement with a polyphyletic origin of tRNA import. Moreover, our increased understanding of the tRNA-import pathway has been exploited recently to rescue dysfunctions associated with mitochondrial tRNA mutations.

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

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