Mitochondrial Protein Synthesis, Import, and Assembly

Abstract

The mitochondrion is arguably the most complex organelle in the budding yeast cell cytoplasm. It is essential for viability as well as respiratory growth. Its innermost aqueous compartment, the matrix, is bounded by the highly structured inner membrane, which in turn is bounded by the intermembrane space and the outer membrane. Approximately 1000 proteins are present in these organelles, of which eight major constituents are coded and synthesized in the matrix. The import of mitochondrial proteins synthesized in the cytoplasm, and their direction to the correct soluble compartments, correct membranes, and correct membrane surfaces/topologies, involves multiple pathways and macromolecular machines. The targeting of some, but not all, cytoplasmically synthesized mitochondrial proteins begins with translation of messenger RNAs localized to the organelle. Most proteins then pass through the translocase of the outer membrane to the intermembrane space, where divergent pathways sort them to the outer membrane, inner membrane, and matrix or trap them in the intermembrane space. Roughly 25% of mitochondrial proteins participate in maintenance or expression of the organellar genome at the inner surface of the inner membrane, providing 7 membrane proteins whose synthesis nucleates the assembly of three respiratory complexes.

The Importance of the 45 S Ribosomal Small Subunit-related Complex for Mitochondrial Translation in Trypanosoma brucei

“…It would also be of particular interest to investigate its potential for formation of the translation initiation complex, a function that would imply an ability to recognize start codons and interact with translation factors and the initiator tRNA. In any case, this study shows that the mechanisms of specific translational activation operating in trypanosomes are clearly different from those in yeast (26,27) or mammals (55). The evolutionary processes responsible for bringing up the puzzling complexity, which marks all aspects of the organization and expression of trypanosomes' mitochondrial genome studied so far, did not bypass its translation apparatus.…”

“…The analogous problem of translation initiation on mRNA with the long 5Ј leaders is solved in yeast with the aid of mRNA-specific activators, including members of the PPR protein family (e.g. Pet309, Pet111, Aep2, and Cbp1), which stabilize mRNA and tether it to the inner membrane and facilitate recruitment of the ribosome to the correct start codon (26,27).…”

Knockdown of Sucla2 decreases the viability of mouse spermatocytes by inducing apoptosis through injury of the mitochondrial function of cells

“…Mitochondrial function depends not only on mitochondrial molecules encoded by nuclear DNA (nDNA), but also depends on molecules encoded by mitochondria DNA (mtDNA) [19,20]. The literature shows that many kinds of abnormal expression of mitochondrial proteins are associated with mitochondrial dysfunction, resulting in mitochondrial diseases such as neurodegeneration, cancer, infertility, and ageing [21][22][23].…”

Evidence That Antibiotics Bind to Human Mitochondrial Ribosomal RNA Has Implications for Aminoglycoside Toxicity

“…As mitochondria display similarities with bacteria in their protein expression machinery (52,53), we hypothesized that the mechanism of aminoglycoside binding to the mitochondrial and bacterial ribosomes may be similar. Components of the mitochondrial translational machinery resemble those employed by bacteria, but are distinct from their cytoplasmic counterparts (54).…”