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

• Published in: Science advances Vol. 7; no. 45; p. eabg4119
• Main Authors: Gamero-Quijano, Alonso, Bhattacharya, Shayon, Cazade, Pierre-André, Molina-Osorio, Andrés F, Beecher, Cillian, Djeghader, Ahmed, Soulimane, Tewfik, Dossot, Manuel, Thompson, Damien, Herzog, Grégoire, Scanlon, Micheál D
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science (AAAS) 05.11.2021; American Association for the Advancement of Science
• Subjects: Biochemistry; Biochemistry, Molecular Biology; Biomedicine and Life Sciences; Cell Biology; Chemical Sciences; Life Sciences; or physical chemistry; SciAdv r-articles; Theoretical and
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.abg4119

Programmed cell death via apoptosis is a natural defence against excessive cell division, crucial for fetal development to maintenance of homeostasis and elimination of precancerous and senescent cells. Here, we demonstrate an electrified liquid biointerface that replicates the molecular machinery of the inner mitochondrial membrane at the onset of apoptosis. By mimicking in vivo cytochrome c (Cyt c) interactions with cell membranes, our platform allows us to modulate the conformational plasticity of the protein by simply varying the electrochemical environment at an aqueous-organic interface. We observe interfacial electron transfer between an organic electron donor decamethylferrocene and O , electrocatalyzed by Cyt c. This interfacial reaction requires partial Cyt c unfolding, mimicking Cyt c in vivo peroxidase activity. As proof of concept, we use our electrified liquid biointerface to identify drug molecules, such as bifonazole, that can potentially down-regulate Cyt c and protect against uncontrolled neuronal cell death in neurodegenerative disorders.