N ‐(3‐oxo‐acyl)‐homoserine lactone induces apoptosis primarily through a mitochondrial pathway in fibroblasts

ABSTRACT N‐(3‐oxododecanoyl)‐homoserine lactone (C12) is produced by Pseudomonas aeruginosa to function as a quorum‐sensing molecule for bacteria‐bacteria communication. C12 is also known to influence many aspects of human host cell physiology, including induction of cell death. However, the signaling pathway(s) leading to C12‐triggered cell death is (are) still not completely known. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in “initiator” caspases or “effector” caspases. Our data indicate that C12 selectively induces the mitochondria‐dependent intrinsic apoptotic pathway by quickly triggering mitochondrial outer membrane permeabilization (MOMP). Importantly, the activities of C12 to permeabilize mitochondria is independent of activation of both “initiator” and “effector” caspases. Furthermore, C12 directly induces MOMP in vitro. Overall, our study suggests a mitochondrial apoptotic signaling pathway triggered by C12, in which C12 or its metabolite(s) acts on mitochondria to permeabilize mitochondria, leading to activation of apoptosis.
Source: Cellular Microbiology - Category: Microbiology Authors: Tags: RESEARCH ARTICLE Source Type: research