A mitokondriális citokróm c vizsgálata és metodikai fejlesztés
Csomó Krisztián
Molecular Medicine Division
Dr. Várnai Péter
SE Szülészeti és Nőgyógy. Kl, Üllői úti részleg
2026-11-05 10:00:00
Pathobiochemistry
Dr. Ligeti Erzsébet
Dr. Kukor Zoltán és Dr. Varga Gábor Sándor
Dr. Miklya Ildikó
Dr. Szabó Nóra Zsuzsanna
Dr. Ambrus Attila
Dr. Lendvai Dávid
Dr. Szeri Flóra
The aim of our research was to further our understanding of those mitochondrial processes that determine the oxidation capacity of cytochrome c.
We designed our examinations to be easy to implement as well as easy to replicate.
During our examinations we successfully proved that the membrane bound and free type of cytochrome c differ in their oxidation capacity. Oxidation happens in the case of free cytochrome c. We also determined that this difference is due to bonds formed with phospholipids.
Based on our research of Ca2+ and Mg2+, we determined that these cations significantly increase the oxidation capacity of cyt c. Our research also showed that this increase is due to two mechanisms. Firstly, these cations directly increase the oxidation capacity of cyt c. Secondly, Ca and Mg ions cause the release of the membrane-bound cyt c, which from thereon have the capacity to oxidate glutathione.
Following these experiments, we conducted further experiments to determine the effect of statins on the oxidation of glutathione. For our research we studied both lipophilic (simvastatin) and hydrophilic (pravastatin) to account for their differing side-effects. Our studies showed that lipophilic statin simvastatin had an opposite effect to hydrophilic pravastatin on the oxidation of glutathione: simvastatin increased the oxidation while pravastatin decreased the oxidation of glutathione. Our research showed that statins only affect cytochrome c in its free form. Our earlier results regarding the effect of Ca2+ and Mg2+ on freeing the membrane bound form of cytochrome c (thereby increasing free cytochrome c) become relevant here as well.
Our further studies showed that Mg2+ and simvastatin applied together significantly increased the speed of oxidation of glutathione.
We also found another potential pathway for apoptosis, facilitated by lipophilic statins.
As a consequence of the oxidation of glutathione, the concentration of oxides can significantly increase even without the presence of reactive oxygen species, thereby increasing oxidative stress. We showed this by examining mitochondrial oxygen consumption, both in vitro using bovine cytochrome c and in vivo using rat liver mitochondria.
We plan to conduct further experiments on mitochondrial cytochrome c in cases of neural injury to investigate the apoptosis inducing effect of statins. For this we modified the widely used classical spinal chord injury technique and made it minimally invasive.
