VDAC

VDAC este o porină din membrana mitocondriala cu rol in apoptoză. In plus fata de permeabilitatea voltaj dependenta fata de anioni se pare ca in anumite situatii se produce o crestere majora a permeabilitatii sale cu trecerea unor peptiode cu importanta functionala din mitocondrie in citosol. Exista ipoteza ca diversi factori modulatori cum sunt cei oxidativi pot declansa apoptoză si cu participarea porinei VDAC. Noi dorim sa evaluam asemenea modificari cu importanta functionala ce se produc dupa atacul oxidativ asupra anumitor radicali tirozinice din structura moleculei. Din experimente in vitro şi in vivo, modificarea se produce prin nitrare sau agregare sub acţiunea anionului peroxinitrit. Acesta este produs din oxid nitric si anionul superoxid generate in exces in conditiile expunerii la microrganisme, substante chimice, radiatii electromagnetice ionizante si stress psihic. Fenomenul de generare la nivele inalte de peroxinitrit si acţiunea acestuia asupra moleculelor proteice şi lipidice se numeste stress nitrooxidativ. Nitrarea VDAC este un eveniment cu consecinţe funcţionale majore atât prin fenomenul de oligomerizare cât şi prin posibilele punţi ditirozinice formate sub acţiunea peroxynitritului. Structurile supramoleculare rezultate modifică major structura membranară şi asta în condiţiile stressului nitrooxidativ. Porina VDAC este implicata in multiple patologii ce contin o amplificare a apoptozei mitocondrial induse. The voltage-dependent anion channel (VDAC) is the most abundant protein in the mitochondrial outer membrane (MOM). Due to its localization, VDAC is involved in a wide range of processes, such as passage of ATP out of mitochondria, and particularly plays a central role in apoptosis. Importantly, the assembly of VDAC provides interaction with a wide range of proteins, some implying oligomerization. However, many questions remain as to the VDAC structure, its supramolecular assembly, packing density, and oligomerization in the MOM is unknown. Here we report the so far highest resolution view of VDAC and its native supramolecular assembly. We have studied yeast MOM by high-resolution atomic force microscopy (AFM) in physiological buffer and found VDAC in two distinct types of

The present study was aimed to provide a better understanding of the mitochondria-targeted actions of minocycline (MC), a second-generation tetracycline which has cytoprotective effects. Although the specific mechanisms underlying its activity remained elusive, considerable amounts of data indicated mitochondria as the primary pharmacological target of MC. Previous reports have shown that MC affects the oxygen-uptake rate by isolated mitochondria in