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.