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

Yuya Goto, Reiko Hayashi, Dongchon Kang, Kenichi Yoshida

Research output: Contribution to journalArticlepeer-review

28 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 2006

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Acute loss of transcription factor E2F1 induces mitochondrial biogenesis in HeLa cells'. Together they form a unique fingerprint.

Cite this