Mitochondria regulate the unfolded protein response leading to cancer cell survival under glucose deprivation conditions

Naomi Haga, Sakae Saito, Yoshinori Tsukumo, Junko Sakurai, Aki Furuno, Takashi Tsuruo, Akihiro Tomida

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Cancer cells consume large amounts of glucose because of their specific metabolic pathway. However, cancer cells exist in tumor tissue where glucose is insufficient. To survive, cancer cells likely have the mechanism to elude their glucose addiction. Here we show that functional mitochondria are essential if cancer cells are to avoid glucose addiction. Cancer cells with dysfunctional mitochondria, such as mitochondrial DNA-deficient Ρ;0 cells and electron transport chain blocker-treated cells, were highly sensitive to glucose deprivation. Our data demonstrated that this sensitization was associated with failure of the unfolded protein response (UPR), an adaptive response mediated by the endoplasmic reticulum (ER). This study suggests a link between mitochondria and the ER during the UPR under glucose deprivation conditions and that mitochondria govern cell fate, not only through ATP production and apoptosis regulation, but also through modulating the UPR for cell survival.

Original languageEnglish
Pages (from-to)1125-1132
Number of pages8
JournalCancer science
Volume101
Issue number5
DOIs
Publication statusPublished - 2010 May 1
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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