MITOCHONDRIAL DYSFUNCTION AND OXIDATIVE STRESS

Abstract

Mitochondrial major functions are ATP synthesis, regulation of Ca²⁺ homeostasis, generation of reactive oxygen species and programmed cell death. They assume fundamental critical part in the age of cell enactment signals by means of delivered responsive species, as well as little GTPases, mitogen actuated kinases situated in the external and internal films of mitochondria. Several mutations in mitochondrial DNA lead to synthesis of malfunctional proteins characterized by impaired energy metabolism due to presumed genetically-based oxidative phosphorylation (OXPHOS) dysfunction. These proteins cause clear cellular/organelle pathological changes. During these changes, mitochondrial dysfunction is induced via oxidative damage to DNA, electron transport chain and structural proteins as etiologically important events in development and progression of mitochondrial diseases including malignancies, diabetes, hypertension, inflammation, hepatitis, neuromuscular and neurodegenerative ones.  Literature data suggests several mechanisms of mitochondrial dysfunction. One of the main challenges in the coming years seems to assess timely the functional/structural modulation to mitochondrial proteins and damage to DNA as potential causes or consequences of diseases.  Upon mitochondria dysfunction in oxidative stress mechanistic issues are resolved, use of mitochondria as a pharmacological target holds unforeseen promise in the treatment of diseases.  This report presents a short overview on newest discoveries supporting mechanisms of mitochondria in oxidative stress, inflammatory and apoptosis-based diseases, clinical management and therapeutic failure if any.