Mitochondria regulate the unfolded protein response leading to cancer cell survival under glucose deprivation conditions.
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 rho(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.
Haga
Naomi
N
The Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Saito
Sakae
S
Tsukumo
Yoshinori
Y
Sakurai
Junko
J
Furuno
Aki
A
Tsuruo
Takashi
T
Tomida
Akihiro
A
D045744:Cell Line, Tumor; D002470:Cell Survival; D004579:Electron Transport / Q000502:physiology; D000091342:Endoplasmic Reticulum Chaperone BiP; D005947:Glucose / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D056811:Unfolded Protein Response
D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D005947:Glucose