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PMID: 15509786 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Architectural role of mitochondrial transcription factor A in maintenance of human mitochondrial DNA.

Molecular and cellular biology ·Vol. 24 ·No. 22 ·2004-11-00 ·Pages 9823-34

Kanki T, Ohgaki K, Gaspari M, Gustafsson CM, Fukuoh A, Sasaki N, Hamasaki N, Kang D

Abstract

Mitochondrial transcription factor A (TFAM), a transcription factor for mitochondrial DNA (mtDNA) that also possesses the property of nonspecific DNA binding, is essential for maintenance of mtDNA. To clarify the role of TFAM, we repressed the expression of endogenous TFAM in HeLa cells by RNA interference. The amount of TFAM decreased maximally to about 15% of the normal level at day 3 after RNA interference and then recovered gradually. The amount of mtDNA changed closely in parallel with the daily change in TFAM while in organello transcription of mtDNA at day 3 was maintained at about 50% of the normal level. TFAM lacking its C-terminal 25 amino acids (TFAM-DeltaC) marginally activated transcription in vitro. When TFAM-DeltaC was expressed at levels comparable to those of endogenous TFAM in HeLa cells, mtDNA increased twofold, suggesting that TFAM-DeltaC is as competent in maintaining mtDNA as endogenous TFAM under these conditions. The in organello transcription of TFAM-DeltaC-expressing cells was no more than that in the control. Thus, the mtDNA amount is finely correlated with the amount of TFAM but not with the transcription level. We discuss an architectural role for TFAM in the maintenance of mtDNA in addition to its role in transcription activation.

MeSH Terms
Animals Base Sequence DNA, Mitochondrial/genetics,metabolism DNA-Binding Proteins/chemistry,genetics,metabolism Gene Expression HeLa Cells High Mobility Group Proteins Humans In Vitro Techniques Mice Mitochondria/metabolism Mitochondrial Proteins/chemistry,genetics,metabolism Nuclear Proteins/chemistry,genetics,metabolism RNA Interference RNA, Small Interfering/genetics Recombinant Proteins/chemistry,genetics,metabolism Sequence Deletion Transcription Factors/chemistry,genetics,metabolism Transcription, Genetic
Chemicals
DNA, Mitochondrial DNA-Binding Proteins High Mobility Group Proteins Mitochondrial Proteins Nuclear Proteins RNA, Small Interfering Recombinant Proteins TFAM protein, human Tfam protein, mouse Transcription Factors mitochondrial transcription factor A
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Kanki Tomotake
Department of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Ohgaki Kippei
Gaspari Martina
Gustafsson Claes M
Fukuoh Atsushi
Sasaki Narie
Hamasaki Naotaka
Kang Dongchon
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.22.9823-9834.2004
Published
2004-11-00
Pages
9823-34
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC525493
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.24.22.9823-9834.2004 PMC Full Text View journal details
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