Acute loss of transcription factor E2F1 induces mitochondrial biogenesis in HeLa cells

Yuya Goto, Reiko Hayashi, Dongchon Kang, Kenichi Yoshida

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Here, we sought to clarify the comprehensive cellular response to transcription factor E2F1 expression using short interfering RNA (siRNA)-mediated gene silencing to examine the roles of E2F1. For this purpose, we analyzed global gene expression changes in E2F1 knockdown HeLa cells, where no changes in cell growth or apoptosis were observed. Among the identified genes, the mRNA levels of mitochondria-encoded genes were highly elevated in E2F1 siRNA-treated cells, but not in E2F6 siRNA-treated cells, relative to control siRNA-treated cells. These changes were accompanied by a significant increase in the transcription and replication of mitochondria DNA as well as the induction of nuclear-encoded mitochondrial topoisomerase I (TOP1MT) mRNA in E2F1 knockdown cells, but not in E2F6 knockdown cells, whereas the levels of nuclear-encoded mitochondrial transcription factor A (TFAM) mRNA and protein were unchanged, relative to the levels in control siRNA-treated cells. Time-course experiments demonstrated that the induction of TOP1MT coincided with the timing of E2F1 loss. In addition, E2F1 knockdown cells, but not E2F6 knockdown cells, displayed increased ATP levels along with an accumulation of cytochrome b protein. Finally, RNA interference (RNAi)-mediated reduction in E2F1 knockdown HeLa cells, but not in E2F6 knockdown HeLa cells, resulted in increased anticancer drug sensitivity. Taken together, these data demonstrate a novel physiological aspect of E2F1 in human cancer cells, where activated mitochondrial biogenesis occurs as a consequence of the acute loss of E2F1.

Original languageEnglish
Pages (from-to)923-934
Number of pages12
JournalJournal of cellular physiology
Volume209
Issue number3
DOIs
Publication statusPublished - Dec 1 2006

Fingerprint

E2F1 Transcription Factor
Organelle Biogenesis
HeLa Cells
Small Interfering RNA
Cells
Mitochondria
Genes
Messenger RNA
Type I DNA Topoisomerase
Cytochromes b
Cell growth
Transcription
Gene expression
Proteins
Adenosine Triphosphate
RNA
Apoptosis
DNA
Gene Silencing
RNA Interference

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Acute loss of transcription factor E2F1 induces mitochondrial biogenesis in HeLa cells. / Goto, Yuya; Hayashi, Reiko; Kang, Dongchon; Yoshida, Kenichi.

In: Journal of cellular physiology, Vol. 209, No. 3, 01.12.2006, p. 923-934.

Research output: Contribution to journalArticle

Goto, Yuya ; Hayashi, Reiko ; Kang, Dongchon ; Yoshida, Kenichi. / Acute loss of transcription factor E2F1 induces mitochondrial biogenesis in HeLa cells. In: Journal of cellular physiology. 2006 ; Vol. 209, No. 3. pp. 923-934.
@article{b255aafcdfb34e93825ba07deae557ea,
title = "Acute loss of transcription factor E2F1 induces mitochondrial biogenesis in HeLa cells",
abstract = "Here, we sought to clarify the comprehensive cellular response to transcription factor E2F1 expression using short interfering RNA (siRNA)-mediated gene silencing to examine the roles of E2F1. For this purpose, we analyzed global gene expression changes in E2F1 knockdown HeLa cells, where no changes in cell growth or apoptosis were observed. Among the identified genes, the mRNA levels of mitochondria-encoded genes were highly elevated in E2F1 siRNA-treated cells, but not in E2F6 siRNA-treated cells, relative to control siRNA-treated cells. These changes were accompanied by a significant increase in the transcription and replication of mitochondria DNA as well as the induction of nuclear-encoded mitochondrial topoisomerase I (TOP1MT) mRNA in E2F1 knockdown cells, but not in E2F6 knockdown cells, whereas the levels of nuclear-encoded mitochondrial transcription factor A (TFAM) mRNA and protein were unchanged, relative to the levels in control siRNA-treated cells. Time-course experiments demonstrated that the induction of TOP1MT coincided with the timing of E2F1 loss. In addition, E2F1 knockdown cells, but not E2F6 knockdown cells, displayed increased ATP levels along with an accumulation of cytochrome b protein. Finally, RNA interference (RNAi)-mediated reduction in E2F1 knockdown HeLa cells, but not in E2F6 knockdown HeLa cells, resulted in increased anticancer drug sensitivity. Taken together, these data demonstrate a novel physiological aspect of E2F1 in human cancer cells, where activated mitochondrial biogenesis occurs as a consequence of the acute loss of E2F1.",
author = "Yuya Goto and Reiko Hayashi and Dongchon Kang and Kenichi Yoshida",
year = "2006",
month = "12",
day = "1",
doi = "10.1002/jcp.20802",
language = "English",
volume = "209",
pages = "923--934",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Acute loss of transcription factor E2F1 induces mitochondrial biogenesis in HeLa cells

AU - Goto, Yuya

AU - Hayashi, Reiko

AU - Kang, Dongchon

AU - Yoshida, Kenichi

PY - 2006/12/1

Y1 - 2006/12/1

N2 - Here, we sought to clarify the comprehensive cellular response to transcription factor E2F1 expression using short interfering RNA (siRNA)-mediated gene silencing to examine the roles of E2F1. For this purpose, we analyzed global gene expression changes in E2F1 knockdown HeLa cells, where no changes in cell growth or apoptosis were observed. Among the identified genes, the mRNA levels of mitochondria-encoded genes were highly elevated in E2F1 siRNA-treated cells, but not in E2F6 siRNA-treated cells, relative to control siRNA-treated cells. These changes were accompanied by a significant increase in the transcription and replication of mitochondria DNA as well as the induction of nuclear-encoded mitochondrial topoisomerase I (TOP1MT) mRNA in E2F1 knockdown cells, but not in E2F6 knockdown cells, whereas the levels of nuclear-encoded mitochondrial transcription factor A (TFAM) mRNA and protein were unchanged, relative to the levels in control siRNA-treated cells. Time-course experiments demonstrated that the induction of TOP1MT coincided with the timing of E2F1 loss. In addition, E2F1 knockdown cells, but not E2F6 knockdown cells, displayed increased ATP levels along with an accumulation of cytochrome b protein. Finally, RNA interference (RNAi)-mediated reduction in E2F1 knockdown HeLa cells, but not in E2F6 knockdown HeLa cells, resulted in increased anticancer drug sensitivity. Taken together, these data demonstrate a novel physiological aspect of E2F1 in human cancer cells, where activated mitochondrial biogenesis occurs as a consequence of the acute loss of E2F1.

AB - Here, we sought to clarify the comprehensive cellular response to transcription factor E2F1 expression using short interfering RNA (siRNA)-mediated gene silencing to examine the roles of E2F1. For this purpose, we analyzed global gene expression changes in E2F1 knockdown HeLa cells, where no changes in cell growth or apoptosis were observed. Among the identified genes, the mRNA levels of mitochondria-encoded genes were highly elevated in E2F1 siRNA-treated cells, but not in E2F6 siRNA-treated cells, relative to control siRNA-treated cells. These changes were accompanied by a significant increase in the transcription and replication of mitochondria DNA as well as the induction of nuclear-encoded mitochondrial topoisomerase I (TOP1MT) mRNA in E2F1 knockdown cells, but not in E2F6 knockdown cells, whereas the levels of nuclear-encoded mitochondrial transcription factor A (TFAM) mRNA and protein were unchanged, relative to the levels in control siRNA-treated cells. Time-course experiments demonstrated that the induction of TOP1MT coincided with the timing of E2F1 loss. In addition, E2F1 knockdown cells, but not E2F6 knockdown cells, displayed increased ATP levels along with an accumulation of cytochrome b protein. Finally, RNA interference (RNAi)-mediated reduction in E2F1 knockdown HeLa cells, but not in E2F6 knockdown HeLa cells, resulted in increased anticancer drug sensitivity. Taken together, these data demonstrate a novel physiological aspect of E2F1 in human cancer cells, where activated mitochondrial biogenesis occurs as a consequence of the acute loss of E2F1.

UR - http://www.scopus.com/inward/record.url?scp=33750534156&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750534156&partnerID=8YFLogxK

U2 - 10.1002/jcp.20802

DO - 10.1002/jcp.20802

M3 - Article

C2 - 16972274

AN - SCOPUS:33750534156

VL - 209

SP - 923

EP - 934

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 3

ER -