title: 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.
authors.affiliation: Genetic Engineering, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Calcutta 700032, India.
authors.forename: Bidesh
authors.initials: B
authors.lastname: Mahata
authors.forename: Saikat
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Sumita
authors.initials: S
authors.lastname: Mishra
authors.forename: Arun
authors.initials: A
authors.lastname: Bandyopadhyay
authors.forename: Samit
authors.initials: S
authors.lastname: Adhya
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019069:Cell Respiration; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000378:metabolism; D007895:Leishmania tropica; D017243:MERRF Syndrome / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009154:Mutation; D010101:Oxygen Consumption; D014176:Protein Biosynthesis; D015800:Protozoan Proteins / Q000378:metabolism*; D012357:RNA, Transfer, Lys / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014162:Transfection
chemical_list: D051242:Caveolin 1; D024101:Mitochondrial Proteins; D015800:Protozoan Proteins; D012357:RNA, Transfer, Lys; D016601:RNA-Binding Proteins; D003576:Electron Transport Complex IV