The neurotoxic secreted phospholipase A₂ from the Vipera a. ammodytes venom targets cytochrome c oxidase in neuronal mitochondria.

ABSTRACT: The β-neurotoxic secreted phospholipases A₂ (sPLA₂s) block neuro-muscular transmission by poisoning nerve terminals. Damage inflicted by such sPLA₂s (β-ntx) on neuronal mitochondria is characteristic, very similar to that induced by structurally homologous endogenous group IIA sPLA₂ when its activity is elevated, as, for example, in the early phase of Alzheimer's disease. Using ammodytoxin (Atx), the β-ntx from the venom of the nose-horned viper (Vipera a. ammodytes), the sPLA₂ receptor R25 has been detected in neuronal mitochondria. This receptor has been purified from porcine cerebral cortex mitochondria by a new Atx-affinity-based chromatographic procedure. Mass spectrometry analysis revealed R25 to be the subunit II of cytochrome c oxidase (CCOX), an essential constituent of the respiratory chain complex. CCOX was confirmed as being the first intracellular membrane receptor for sPLA₂ by alternative Atx-affinity-labellings of purified CCOX, supported also by the encounter of Atx and CCOX in PC12 cells. This discovery suggests the explanation of the mechanism by which β-ntx hinders production of ATP in poisoned nerve endings. It also provides a new insight into the potential function and dysfunction of endogenous GIIA sPLA₂ in mitochondria.

SUBMITTER: Sribar J 

PROVIDER: S-EPMC6342964 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature