Methods for expressing and targeting mitochondrial-DNA-encoded peptides and uses thereof

A method for treating a mitochondrial disorder in a subject in need of treatment therefor, comprising administering to the subject a mitochondrial-DNA-encoded (mtDNA-encoded) peptide in an amount effective to treat the mitochondrial disorder.

An expression vector that is useful for introducing a functional peptide encoded by a mitochondrial DNA (mtDNA) sequence into a mitochondrion, comprising:

• (a) a nucleic acid sequence encoding ATPase 6 subunit of F0F1-ATP synthase or ND4 subunit of complex I, wherein the nucleic acid sequence is compatible with the universal genetic code;
• and
• (b) a nucleic acid sequence encoding a mitochondrial-targeting signal, wherein the mitochondrial-targeting signal is selected from the group consisting of the N-terminal region of human cytochrome c oxidase subunit VIII, the N-terminal region of the P1 isoform of subunit c of human ATP synthase, and the N-terminal region of the aldehyde dehydrogenase targeting sequence.

A eukaryotic cell transformed by an expression vector that is useful for introducing a functional peptide encoded by a non-nuclear nucleic acid sequence into an organelle, wherein the eukaryotic cell is derived from algae, an animal, a multicellular or other non-yeast fungus, or protozoa, and the expression vector comprises:

• (a) a non-nuclear nucleic acid sequence encoding the peptide, wherein the nucleic acid sequence is compatible with the universal genetic code;
• and
• (b) a nucleic acid sequence encoding an organelle-targeting signal.

A eukaryotic cell transformed by an expression vector that is useful for introducing a functional peptide encoded by a mitochondrial DNA (mtDNA) sequence into an organelle, wherein the eukaryotic cell is derived from algae, an animal, a multicellular or other non-yeast fungus, a plant, or protozoa, and the expression vector comprises:

• (a) an mtDNA sequence encoding the peptide, wherein the mtDNA sequence is compatible with the universal genetic code;
• and
• (b) a nucleic acid sequence encoding an organelle-targeting signal.