Modulating the pro-apoptotic activity of cytochrome c at a biomimetic electrified interface

Area of Science:

• Biophysics
• Biochemistry
• Cell Biology

Background:

• Programmed cell death (apoptosis) is vital for development and disease prevention.
• Cytochrome c (Cyt c) plays a key role in apoptosis, localized in the inner mitochondrial membrane.
• Dysregulation of apoptosis contributes to diseases like neurodegeneration.

Purpose of the Study:

• To develop an electrified liquid biointerface that mimics the inner mitochondrial membrane.
• To investigate the role of electrochemical environment in modulating cytochrome c (Cyt c) activity.
• To identify potential therapeutic agents for neurodegenerative disorders by targeting Cyt c.

Main Methods:

• Constructed an electrified liquid biointerface at an aqueous-organic interface.
• Mimicked in vivo Cyt c interactions with cell membranes.
• Varied the electrochemical environment to modulate Cyt c conformational plasticity.
• Observed interfacial electron transfer catalyzed by Cyt c, requiring partial protein unfolding.
• Utilized the biointerface to screen for drug molecules affecting Cyt c activity.

Main Results:

• The electrified biointerface successfully replicated key aspects of the inner mitochondrial membrane's molecular machinery.
• Cyt c's conformational plasticity and peroxidase activity were modulated by the electrochemical environment.
• Interfacial electron transfer between decamethylferrocene and O2 was electrocatalyzed by Cyt c.
• Partial unfolding of Cyt c was necessary for its observed peroxidase activity at the interface.
• The drug bifonazole was identified as a potential Cyt c down-regulator.

Conclusions:

• The electrified liquid biointerface provides a novel platform for studying apoptosis-related molecular mechanisms.
• Modulating the electrochemical environment offers a new approach to control Cyt c activity.
• This platform can be used to discover drugs that protect against uncontrolled cell death in neurodegenerative diseases.