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PMID: 19460293 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Recombinant mitochondrial transcription factor A with N-terminal mitochondrial transduction domain increases respiration and mitochondrial gene expression.

Mitochondrion ·Vol. 9 ·No. 3 ·2009-06-00 ·Pages 196-203

Iyer S, Thomas RR, Portell FR, Dunham LD, Quigley CK, Bennett JP

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.

MeSH Terms
Adult Cell Line DNA-Binding Proteins/genetics,metabolism Gene Expression Genes, Mitochondrial Humans Male Mitochondria/metabolism Mitochondrial Proteins/biosynthesis,genetics,metabolism Protein Sorting Signals Protein Transport Respiration Transcription Factors/genetics,metabolism
Chemicals
DNA-Binding Proteins Mitochondrial Proteins Protein Sorting Signals Transcription Factors mitochondrial transcription factor A
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Iyer Shilpa
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.
Thomas Ravindar R
Portell Francisco R
Dunham Lisa D
Quigley Caitlin K
Bennett James P
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Article Info
Journal
Mitochondrion
Abbr.
Mitochondrion
ISSN
1872-8278
DOI
10.1016/j.mito.2009.01.012
Published
2009-06-00
Epub
2009-00-04
Pages
196-203
Language
English
Region
Netherlands
NLM ID
100968751
PMCID
PMC2783715
Subset
IM
Grants
NIA NIH HHS · R42 AG023443-03 · United States
NIA NIH HHS · AG023443 · United States
NIA NIH HHS · R41 AG023443 · United States
NINDS NIH HHS · P50 NS039788 · United States
NINDS NIH HHS · P50 NS039788-090006 · United States
NIA NIH HHS · R41 AG023443-01 · United States
NINDS NIH HHS · P50 NS039788-080006 · United States
NINDS NIH HHS · NS39788 · United States
NIA NIH HHS · R42 AG023443-02 · United States
NIDCD NIH HHS · K18 DC009121 · United States
NIDCD NIH HHS · K18 DC009121-01 · United States
NIA NIH HHS · R42 AG023443 · United States
External Links
PubMed source DOI: 10.1016/j.mito.2009.01.012 PMC Full Text View journal details
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