Mitochondrial involvement in aspirin-induced apoptosis in yeast

Abstract

We have previously reported that aspirin induces apoptosis in manganese superoxide dismutase (MnSOD)-deficient Saccharomyces cerevisiae cells when cultivated on the non-fermentable carbon source ethanol. Here, we investigated the role of mitochondria in aspirin-induced apoptosis. We report that aspirin had an inhibitory effect on cellular respiration, and caused the release of most of the mitochondrial cytochrome c and a dramatic drop in the mitochondrial membrane potential (DY m ). Also, aspirin reduced the intracellular cytosolic pH in the MnSODdeficient cells growing in ethanol medium, but this did not seem to be the initial trigger that committed these cells to aspirin-induced apoptosis. Furthermore, loss of DY m was not required for aspirin-induced release of cytochrome c, since the initial release of cytochrome c occurred prior to the disruption of the DY m . It is thus possible that cytochrome c release does not involve the early onset of the mitochondrial permeability transition, but only an alteration of the permeability of the outer mitochondrial membrane.

Subunits Rip1p and Cox9p of the respiratory chain contribute to diclofenac-induced mitochondrial dysfunction

“…These results indicate a clear link between mitochondrial respiration, ROS formation and diclofenac toxicity. Interestingly, another NSAID, aspirin, has also been linked to mitochondrial dysfunction in yeast, leading to apoptosis (Sapienza et al, 2008).…”

The Proapoptotic Effect of Traditional and Novel Nonsteroidal Anti-Inflammatory Drugs in Mammalian and Yeast Cells

“…These observations indicate that cytochrome c release is a critical mediatory mechanism of apoptotic cell death induced by NSAIDs [39]. In fact, it has also been shown that aspirin-induced apoptosis of S. cerevisiae cells deficient in manganese superoxide dismutase (MnSOD) and cultivated in nonfermentable ethanol medium is preceded by the early release of cytochrome c , followed by a drastic fall in ΔΨ m [93]. …”

“…Likewise, it has been shown that the mitochondria of S. cerevisiae cells constitute a critical target of NSAIDs such as aspirin [32], the proapoptotic effects of which were shown to be associated with inhibition of the electron transport chain [93]. Similarly, Van Leeuwen and coworkers [33] observed that growth inhibition and apoptosis of S. cerevisiae cells caused by treatment with the NSAID diclofenac were due to mitochondrial dysfunctional events involving the inhibition of the electron transport chain.…”

Interaction of plant cell signaling molecules, salicylic acid and jasmonic acid, with the mitochondria of Helicoverpa armigera

“…SA inhibited the activities of NADH dehydrogenase and succinate dehydrogenase in H. armigera. Aspirin, a derivative of SA, has been reported as a uncoupler of oxidative phosphorylation in Yeast (Sapienza et al 2008), and inhibitor of electron transport chain at complex I and complex II in rat liver mitochondria (Somsundaram et al 1997). According to Battaglia et al (2005), the most probable site for binding the SA is Fe 3+ of Fe-S clusters of mitochondrial complexes.…”