title: Recombinant mitochondrial transcription factor A with N-terminal mitochondrial transduction domain increases respiration and mitochondrial gene expression.
abstract: We developed a scalable procedure to produce human mitochondrial transcription factor A (TFAM) modified with an N-terminal protein transduction domain (PTD) and mitochondrial localization signal (MLS) that allow it to cross membranes and enter mitochondria through its "mitochondrial transduction domain" (MTD=PTD+MLS). Alexa488-labeled MTD-TFAM rapidly entered the mitochondrial compartment of cybrid cells carrying the G11778A LHON mutation. MTD-TFAM reversibly increased respiration and levels of respiratory proteins. In vivo treatment of mice with MTD-TFAM increased motor endurance and complex I-driven respiration in mitochondria from brain and skeletal muscle. MTD-TFAM increases mitochondrial bioenergetics and holds promise for treatment of mitochondrial diseases involving deficiencies of energy production.
authors.affiliation: Center for the Study of Neurodegenerative Diseases and The Morris K. Udall Parkinson's Disease Research Center of Excellence, University of Virginia, PO Box 800394, Charlottesville, VA 22908, United States.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Iyer
authors.forename: Ravindar R
authors.initials: RR
authors.lastname: Thomas
authors.forename: Francisco R
authors.initials: FR
authors.lastname: Portell
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Dunham
authors.forename: Caitlin K
authors.initials: CK
authors.lastname: Quigley
authors.forename: James P
authors.initials: JP
authors.lastname: Bennett
mesh_terms: D000328:Adult; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D050259:Genes, Mitochondrial; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D021382:Protein Sorting Signals; D021381:Protein Transport; D012119:Respiration; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D021382:Protein Sorting Signals; D014157:Transcription Factors; C422562:mitochondrial transcription factor A