Related Experiment Video

Updated: Jul 5, 2026

Monitoring Dynamic Changes In Mitochondrial Calcium Levels During Apoptosis Using A Genetically Encoded Calcium Sensor
06:26

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

Published on: April 1, 2011

BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis

Luca Scorrano1, Scott A Oakes, Joseph T Opferman

  • 1Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Department of Pathology and Medicine, Harvard Medical School, Boston, MA 02115, USA.

Science (New York, N.Y.)
|March 8, 2003
PubMed

Insights

Proapoptotic proteins BAX and BAK are crucial for initiating apoptosis by regulating calcium levels in the endoplasmic reticulum (ER) and mitochondria. Their presence is essential for specific cell death pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • BAX and BAK are key proapoptotic proteins involved in initiating mitochondrial dysfunction.
  • These proteins also localize to the endoplasmic reticulum (ER), suggesting a role beyond mitochondria.

Purpose of the Study:

  • To investigate the role of BAX and BAK in regulating ER calcium homeostasis and its impact on apoptosis.
  • To determine how BAX and BAK localization affects sensitivity to different apoptotic stimuli.

Main Methods:

  • Utilized mouse embryonic fibroblasts deficient for BAX and BAK (DKO cells).
  • Assessed ER calcium concentrations ([Ca2+]er) and mitochondrial calcium uptake.
  • Restored SERCA expression to correct calcium dysregulation.
  • Investigated apoptosis induction using various agents, including those releasing calcium from intracellular stores and BH3-only signals.
  • Examined the requirement for ER calcium release and mitochondrial BAX/BAK for apoptosis.

Main Results:

  • DKO cells exhibited reduced resting [Ca2+]er and impaired mitochondrial calcium uptake.
  • SERCA expression restored [Ca2+]er and mitochondrial calcium uptake, re-sensitizing DKO cells to certain apoptotic stimuli.
  • Targeting BAX to mitochondria restored apoptosis only to BH3-only signals.
  • Many intrinsic apoptotic signals required both ER calcium release and mitochondrial BAX/BAK.

Conclusions:

  • BAX and BAK act as essential gateways for specific apoptotic signals at both the ER and mitochondria.
  • ER calcium regulation by BAX and BAK is critical for initiating apoptosis in response to certain cellular stresses.
  • The localization of BAX and BAK dictates their role in mediating distinct apoptotic pathways.

More Related Videos

Examining BCL-2 Family Function with Large Unilamellar Vesicles08:35

Examining BCL-2 Family Function with Large Unilamellar Vesicles

Published on: October 5, 2012

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila13:21

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

Published on: November 27, 2016

Related Concept Videos

Cell Motility through Blebbing01:16

Cell Motility through Blebbing

Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Cellular Injury IV: Necrosis01:16

Cellular Injury IV: Necrosis

Necrosis is a form of irreversible cell death caused by severe injury such as ischemia, toxins, or trauma. Unlike programmed cell death, it is an uncontrolled, pathological process that typically provokes inflammation in surrounding tissues.Pathophysiologic ChangesNecrosis begins when cells sustain critical damage, leading to swelling of organelles, particularly mitochondria, and rapid ATP depletion. As energy levels decline, membrane ion pumps fail, leading to calcium influx and eventually,...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...