Functional Delivery of a Cytosolic tRNA into Mutant Mitochondria of Human Cells

Abstract

Many maternally inherited and incurable neuromyopathies are caused by mutations in mitochondrial (mt) transfer RNA (tRNA) genes. Kinetoplastid protozoa, including Leishmania , have evolved specialized systems for importing nucleus-encoded tRNAs into mitochondria. We found that the Leishmania RNA import complex (RIC) could enter human cells by a caveolin-1–dependent pathway, where it induced import of endogenous cytosolic tRNAs, including tRNA Lys , and restored mitochondrial function in a cybrid harboring a mutant mt tRNA Lys ( MT-TK ) gene. The use of protein complexes to modulate mitochondrial function may help in the management of such genetic disorders.