Open AccessMitochondria regulate the unfolded protein response leading to cancer cell survival under glucose deprivation conditions
Author(s) -
Haga Naomi,
Saito Sakae,
Tsukumo Yoshinori,
Sakurai Junko,
Furuno Aki,
Tsuruo Takashi,
Tomida Akihiro
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01525.x
Subject(s) - unfolded protein response , mitochondrion , endoplasmic reticulum , cancer cell , microbiology and biotechnology , apoptosis , cancer , biology , cell , glucose regulated protein , biochemistry , genetics
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. ( Cancer Sci 2010; 101: 1125–1132)