The mitochondrial permeability transition (MPT) plays an important role in cell death. The MPT is triggered by calcium and promoted by oxidative stress, which is often catalyzed by iron. We investigated the induction of the MPT by physiological concentrations of iron. Isolated rat liver mitochondria were initially stabilized with EDTA and bovine serum albumin and energized by succinate or malate/pyruvate. The MPT was induced by 20μM calcium or ferrous chloride. We measured mitochondrial swelling, the inner membrane potential, NAD(P)H oxidation, iron and calcium in the recording medium. Iron effectively triggered the MPT; this effect differed from non-specific oxidative damage and required some residual EDTA in the recording medium. Evidence in the literature suggested two mechanisms of action for the iron: NAD(P)H oxidation due to loading of the mitochondrial antioxidant defense systems and uptake of iron to the mitochondrial matrix via a calcium uniporter. Both of these events occurred in our experiments but were only marginally involved in the MPT induced by iron. The primary mechanism observed in our experiments was the displacement of adventitious/endogenous calcium from the residual EDTA by iron. Although artificially created, this interplay between iron and calcium can well reflect conditions in vivo and could be considered as an important mechanism of iron toxicity in the cells.

• MeSH
• karbonylkyanid-p-trifluormethoxyfenylhydrazon farmakologie   MeSH
• krysa rodu Rattus MeSH
• NAD metabolismus   MeSH
• oxidace-redukce MeSH
• potkani Wistar MeSH
• přechodový pór mitochondriální permeability MeSH
• transportní proteiny mitochondriální membrány fyziologie   MeSH
• vápník metabolismus   MeSH
• železo farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• karbonylkyanid-p-trifluormethoxyfenylhydrazon MeSH
• NAD MeSH
• přechodový pór mitochondriální permeability MeSH
• transportní proteiny mitochondriální membrány MeSH
• vápník MeSH
• železo MeSH