N‐(3‐Oxo‐acyl)‐homoserine lactone induces apoptosis primarily through a mitochondrial pathway in fibroblasts |
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| Authors: | Guoping Zhao Christian Schwarzer Nicole S. Stivers Aaron G. Whitt Shuhan Meng Joseph A. Burlison Terry E. Machen Chi Li |
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| Affiliation: | 1. Molecular Targets Program, James Graham Brown Cancer Center, Departments of Medicine, Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA;2. Institute of Technical Biology and Agriculture Engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China;3. Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA;4. Structural Biology Program, James Graham Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, KY, USA |
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| Abstract: | N‐(3‐Oxododecanoyl)‐l ‐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 signalling pathway(s) leading to C12‐triggered cell death is (are) still not completely known. To clarify cell death signalling induced by C12, we examined mouse embryonic fibroblasts 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 permeabilisation. Importantly, the activities of C12 to permeabilise mitochondria are independent of activation of both “initiator” and “effector” caspases. Furthermore, C12 directly induces mitochondrial outer membrane permeabilisation in vitro. Overall, our study suggests a mitochondrial apoptotic signalling pathway triggered by C12, in which C12 or its metabolite(s) acts on mitochondria to permeabilise mitochondria, leading to activation of apoptosis. |
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| Keywords: | homoserine lactone apoptosis caspase mitochondria |
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