Related Experiment Video
Updated: Jun 2, 2026
Methods to Study Lipid Alterations in Neutrophils and the Subsequent Formation of Neutrophil Extracellular Traps
Published on: March 29, 2017
Cholesterol, cardiolipin, and mitochondria permeabilisation
Safa Lucken-Ardjomande Hasler1
1MRC-Laboratory of Molecular Biology, Neurobiology Division, Cambridge, UK. slucken@mrc-lmb.cam.ac.uk
Abstract:
Apoptosis is a form of programmed cell death required for the development and for the proper functioning of multicellular organisms. It is defined by a combination of morphological and biochemical modifications that result from the activation of a family of proteases called caspases. Several pathways can lead to caspase activation and they often involve the release of apoptogenic factors normally sequestered in the mitochondrial intermembrane space. Complete release of mitochondrial pro-apoptotic factors ultimately results in cell death, whether in a caspase-dependent or independent manner. A tight control of mitochondrial permeability is therefore essential. Mutations of regulators of the process, such as proteins of the Bcl-2 family, have indeed been reported in many cancers. In addition, the contributions of lipids, both as regulators of protein activities and as components of the pore itself, are starting to be unravelled. Early on, the role of the mitochondria-specific phospholipid cardiolipin as a targeting signal for pro-apoptotic proteins of the Bcl-2 family was discovered. This role was then expanded since it was shown that cardiolipin also supports conformational changes undergone by proteins of the Bcl-2 family, serves as a docking station for additional pro-apoptotic factors, and is essential for the permeabilisation of synthetic liposomes by activated Bax and Bak. More recently, cholesterol, whose level is increased in most cancer cells, was shown to contribute to their resistance to cytotoxic stresses. Reducing cholesterol levels might therefore represent an interesting novel target to sensitize cancer cells to chemotherapeutic agents.
Insights
Programmed cell death, or apoptosis, is crucial for organism development. Targeting mitochondrial cholesterol levels may enhance cancer chemotherapy effectiveness by sensitizing cancer cells.
Area of Science:
- Cellular Biology
- Biochemistry
- Cancer Research
Background:
- Apoptosis is programmed cell death, essential for multicellular organisms, involving caspases and mitochondrial factors.
- Mitochondrial permeability control is vital, with Bcl-2 family proteins regulating this process and mutations linked to cancer.
- Lipids, including cardiolipin and cholesterol, play significant roles in regulating apoptotic protein activity and membrane permeabilization.
Purpose of the Study:
- To explore the role of lipids, specifically cardiolipin and cholesterol, in regulating apoptosis.
- To investigate the contribution of cholesterol to cancer cell resistance to cytotoxic stress.
- To evaluate cholesterol reduction as a potential strategy to sensitize cancer cells to chemotherapy.
Main Methods:
- Review of existing literature on apoptosis, mitochondrial permeability, and lipid involvement.
- Analysis of the known functions of cardiolipin in targeting and activating pro-apoptotic proteins.
- Examination of studies linking cholesterol levels to cancer cell resistance and chemosensitivity.
Main Results:
- Cardiolipin acts as a targeting signal, supports protein conformational changes, and is essential for liposome permeabilization by Bax and Bak.
- Elevated cholesterol levels in cancer cells contribute to their resistance against cytotoxic stresses.
- The involvement of lipids in apoptosis is increasingly recognized, expanding beyond protein interactions.
Conclusions:
- Cardiolipin plays multifaceted roles in the apoptotic process, influencing protein interactions and membrane permeabilization.
- Cholesterol's role in promoting cancer cell resistance highlights it as a potential therapeutic target.
- Reducing cholesterol could be a novel strategy to improve the efficacy of chemotherapeutic agents in cancer treatment.
More Related Videos
Related Concept Videos
01:28The Inner Mitochondrial Membrane
01:26Membrane Fluidity
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is a relatively...
01:23Membrane Fluidity
01:21Structure of Porins
01:18Membrane Domains
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the anterior...
01:45Mitochondrial Membranes