Related Experiment Video

Updated: Aug 17, 2026

Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
13:40

Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms

Published on: July 7, 2011

Regulation of Ca2+-induced permeability transition by Bcl-2 is antagonized by Drpl and hFis1

Dejuan Kong1, Liping Xu, Yingjie Yu

  • 1Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Molecular and Cellular Biochemistry
|July 14, 2005
PubMed

Insights

Mitochondrial fission proteins Drp1 and hFis1 reduce calcium retention, promoting cell death. The anti-death protein Bcl-2 antagonizes this by interacting with hFis1, suggesting Bcl-2 also regulates mitochondrial fission.

Area of Science:

  • Mitochondrial biology
  • Cell death regulation
  • Protein-protein interactions

Background:

  • Mitochondrial permeability transition (MPT) pore opening is critical for cell survival, and its uncontrolled activation leads to cell death.
  • The anti-death protein Bcl-2 inhibits MPT by enhancing mitochondrial calcium accumulation and retention capacity (CRC).

Purpose of the Study:

  • To investigate the antagonistic effects of mitochondrial fission proteins dynamin-related protein (Drp1) and human mitochondrial fission protein (hFis1) on Bcl-2.
  • To elucidate the role of Drp1 and hFis1 in regulating MPT and calcium homeostasis.
  • To explore the interaction between Bcl-2 and the mitochondrial fission machinery.

Main Methods:

  • Assessing mitochondrial calcium retention capacity (CRC) to evaluate MPT.
  • Investigating protein-protein interactions between Bcl-2, Drp1, and hFis1.
  • Analyzing the impact of Drp1/hFis1 on MPT and CRC.

Main Results:

  • Drp1, with hFis1, reduces mitochondrial calcium retention capacity (CRC), sensitizing cells to MPT.
  • The antagonism between Bcl-2 and Drp1 involves mutually exclusive interactions with hFis1.
  • Mitochondrial fission mediated by Drp1/hFis1 is linked to the reduction in CRC.

Conclusions:

  • Bcl-2 may directly or indirectly regulate mitochondrial fission, extending its known role in apoptosis control.
  • Drp1 and hFis1 antagonize Bcl-2's protective function against MPT.
  • Understanding these protein interactions offers new insights into cell death and survival pathways.

More Related Videos

Development and Application of Rapamycin-regulated Tyrosine Phosphatases06:56

Development and Application of Rapamycin-regulated Tyrosine Phosphatases

Published on: September 6, 2024

Related Concept Videos

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...
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...