Current Medicinal Chemistry - Volume 22, Issue 20, 2015

In liver, cysteamine in all probability represents a “low-capacity, high-affinity” scavenger of ROS. The available body of evidence suggests that reduced cysteamine and oxidized cystamine exist in equilibrium and that this ratio acts as an active redox sensor within the cell much like GSH. During normal liver homeostasis cysteamine’s antioxidant properties are evident. Highly metabolic and/or pro-oxidative conditions, such Read More

Many aspects of adipose tissue pathophysiology in metabolic diseases have been described in the last years. One of such aspects is certainly hypoxia, which was shown to develop in adipose tissue of obese individuals and animal models. Recent data suggest two main factors for adipose tissue hypoxia: adipocyte hypertrophy and vascular dysfunction. In addition, glycation was also shown to induce morphological and funct Read More

Mitochondria are organelles which play an important role not only in cellular metabolism but also in controlling pathways related with cell death, ionic and redox regulation. Alterations in mitochondrial metabolism are implicated in a variety of diseases, including cancer. Cellular and mitochondrial metabolism are both altered during the different stages of tumor development. As cancer cells have altered metabolic pr Read More

Neuronal homeostasis is critically dependent on healthy mitochondria. Mutations in mitochondrial DNA (mtDNA), in nuclear-encoded mitochondrial components, and age-dependent mitochondrial damage, have all been connected with neurological disorders. These in clude not only typical mitochondrial syndromes with neurological features such as encephalomyopathy, myoclonic epilepsy, neuropathy and ataxia; but also s Read More

Mitochondria are key players in the maintenance of cellular homeostasis, as they generate ATP via OXPHOS. As such, disruption in mitochondrial homeostasis is closely associated with disease states, caused by subtle alterations in the function of tissues or by major defects, particularly evident in tissues with high metabolic demands. Adaptations in mitochondrial copy number or mitochondrial mass, and the induction of genes i Read More

In the last twenty years, numerous reports provided solid evidence on the involvement of the mitochondrial permeability transition pore (PTP) in myocardial injury caused by ischemia and reperfusion. Indeed, significant cardioprotection is obtained by reducing the open probability of the PTP. This goal has been achieved by pharmacological and genetic interventions aimed at inhibiting cyclophilin D (CyPD), a regulatory protein Read More

Mitochondrial toxicity is rapidly gaining the interest of researchers and practitioners as a prominent liability in drug discovery and development, accounting for a growing proportion of preclinical drug attrition and post-market withdrawals or black box warnings by the U.S. FDA. To date, the focus of registries of drugs that elicit mitochondrial toxicity has been largely restricted to those that either inhibit the mitochondrial elect Read More

Mitochondria are responsible for coordinating cellular energy production in the vast majority of somatic cells, and every cell type in a specific state can have a distinct metabolic signature. The metabolic requirements of cells from different tissues changes as they proliferate/differentiate, and cellular metabolism must match these demands. Proliferating cells, namely cancer cells and stem cells, tend to prefer glycolysis rather t Read More