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Updated: Sep 20, 2026

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro
Published on: July 17, 2018
The tumor suppressor cybL, a component of the respiratory chain, mediates apoptosis induction
Timur Albayrak1, Volker Scherhammer, Nicole Schoenfeld
1Max-Planck-Institute for Biochemistry, 82152 Martinsried, Germany.
Abstract:
A genetic screen was established to clone apoptosis-inducing genes in a high-throughput format. It led to the isolation of several proapoptotic genes whose proteins are localized to mitochondria. One of the isolated genes is cytochrome bL (cybL also known as SDHC, CII-3, or QPs-1), a component of the respiratory chain complex II. It was further investigated because both cybL and another component of complex II, cybS, have recently been identified as tumor suppressor proteins, some of which act by controlling apoptosis. Our studies reveal that cell death induction by cybL expression is concomitant with a transient inhibition of complex II and the generation of reactive oxygen species. Importantly, cells that are constitutively deficient in cybL are resistant to a variety of proapoptotic cytostatic drugs and to the effects of the Fas receptor. Our results therefore identify complex II as a sensor for apoptosis induction and could explain the unexpected observation that complex II is inactivated in tumors.
Insights
Mitochondrial complex II, including cytochrome bL (cybL), acts as a sensor for apoptosis induction. Its deficiency confers resistance to cell death, potentially explaining complex II inactivation in tumors.
Area of Science:
- Cell Biology
- Biochemistry
- Genetics
Background:
- Apoptosis, or programmed cell death, is crucial for development and disease.
- Mitochondria play a central role in regulating apoptosis.
- Components of the respiratory chain, like complex II, are increasingly implicated in cellular regulation.
Purpose of the Study:
- To identify genes that induce apoptosis using a high-throughput genetic screen.
- To investigate the role of cytochrome bL (cybL), a component of respiratory chain complex II, in apoptosis.
- To determine if complex II functions as a sensor for apoptosis induction.
Main Methods:
- High-throughput genetic screening for apoptosis-inducing genes.
- Cloning and characterization of proapoptotic genes, including cybL.
- Analysis of cellular responses to cybL expression and deficiency, including complex II activity, reactive oxygen species (ROS) generation, and drug/Fas receptor sensitivity.
Main Results:
- Isolation of several proapoptotic genes localized to mitochondria, including cybL.
- Expression of cybL induces cell death, accompanied by transient inhibition of complex II and increased ROS production.
- Cells with constitutive cybL deficiency exhibit resistance to proapoptotic drugs and Fas receptor-mediated cell death.
Conclusions:
- Respiratory chain complex II functions as a sensor for apoptosis induction.
- cybL plays a critical role in mediating apoptosis.
- The findings provide a potential explanation for the observed inactivation of complex II in tumors.
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