Antimicrobial cetylpyridinium chloride disrupts the mitochondrial electron transport chain as potently as cyanide, via cardiolipin interference at cytochrome C
People are widely exposed to the antimicrobial cetylpyridinium chloride (CPC) via consumer products, but CPC is a mitochondrial toxicant with potency comparable to that of canonical mitotoxicants. CPC is largely unregulated despite growing usage, bioavailability, and ability to cross the blood-brain barrier. Previously, we showed, in several cell types at non-cytotoxic and exposure-relevant…
Cetylpyridinium chloride (CPC), a widely used antimicrobial found in consumer products, is a potent mitochondrial toxicant, comparable in effect to cyanide. Despite its increasing usage and ability to cross the blood-brain barrier, CPC remains largely unregulated. Previous studies have demonstrated that CPC inhibits ATP and OCR, key indicators of the electron transport chain (ETC) function, in various cell types at non-cytotoxic doses.
The researchers hypothesized that CPC might target specific components of the ETC, cardiolipin, or TCA enzymes, but their investigation found that CPC inhibits multiple ETC complexes, particularly Complex III-cytochrome C-Complex IV. This interference, mediated by electrostatic interactions with cardiolipin, hinders the shuttle of electrons from Complex III to IV.
Despite not altering cardiolipin levels, CPC exhibits mitotoxicity akin to cyanide. These findings provide crucial insights into the biochemical mechanism of action of this ubiquitous compound, paving the way for epidemiological studies, risk analysis, and predictive toxicology.
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