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Updated: Mar 18, 2026

Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor
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Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor

Published on: April 1, 2011

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FATE1 antagonizes calcium- and drug-induced apoptosis by uncoupling ER and mitochondria

Mabrouka Doghman-Bouguerra1, Veronica Granatiero2, Silviu Sbiera3

  • 1Institut de Pharmacologie Moléculaire et Cellulaire CNRS UMR 7275 Sophia Antipolis, Valbonne, France NEOGENEX CNRS International Associated Laboratory, Valbonne, France University of Nice - Sophia Antipolis, Valbonne, France.

EMBO Reports
|July 13, 2016
PubMed

Insights

The cancer-testis antigen FATE1 protein reduces contact between the endoplasmic reticulum (ER) and mitochondria, decreasing cell death signaling. This mechanism helps cancer cells evade apoptosis and resist chemotherapy.

Area of Science:

  • Cell Biology
  • Cancer Biology
  • Molecular Medicine

Background:

  • Programmed cell death is regulated by calcium (Ca2+) transfer from the endoplasmic reticulum (ER) to mitochondria.
  • Dysregulation of this process is implicated in cancer and neurodegenerative diseases.
  • Mitochondria-associated ER membranes (MAM) are key sites for ER-mitochondria Ca2+ transfer.

Purpose of the Study:

  • To investigate the role of FATE1, a cancer-testis antigen, in regulating ER-mitochondria communication and mitochondrial Ca2+ uptake.
  • To determine the impact of FATE1 on cancer cell survival and response to chemotherapy.

Main Methods:

  • Localization studies of FATE1 at MAM.
  • Analysis of ER-mitochondria contact and Ca2+ uptake in adrenocortical carcinoma (ACC) cells with varying FATE1 expression.
  • Assessment of cell sensitivity to apoptotic stimuli and mitotane treatment.
  • Correlation analysis of FATE1 expression with patient survival data.

Main Results:

  • FATE1 localizes to MAM, modulating ER-mitochondria distance and Ca2+ uptake.
  • FATE1 expression in ACC cells decreases ER-mitochondria contact and mitochondrial Ca2+ uptake.
  • FATE1 knockdown reverses these effects.
  • FATE1 reduces sensitivity to pro-apoptotic stimuli and mitotane.
  • High FATE1 expression in ACC tumors correlates with poorer patient survival.

Conclusions:

  • FATE1 acts as a regulator of ER-mitochondria crosstalk, promoting cancer cell survival.
  • Cancer cells utilize FATE1 to escape apoptosis and resist chemotherapy.
  • FATE1 is a potential therapeutic target in adrenocortical carcinoma.
Keywords:
MAMadrenal cortexapoptosisendocrine cancermitochondria

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