👤 Julia Rendon

Conditions that led to the synthesis of iron-sulfur clusters coordinated to tripeptides with a single thiolate ligand were investigated by UV-vis, NMR, EPR, and Mössbauer spectroscopies and by electrochemistry. Increasing concentrations of hydrosulfide correlated with the formation of higher nuclearity iron-sulfur clusters from mononuclear to [2Fe-2S] to [4Fe-4S] and finally to a putative, nitrogenase-like [6Fe-9S] complex. Increased nuclearity was also associated with decreased dynamics and increased stability. The synthesis of higher nuclearity iron-sulfur clusters is compatible with shallow, alkaline bodies of water on the surface of the early Earth, although other niche environments are possible. Because of the plasticity of such complexes, the type of iron-sulfur cluster formed on the prebiotic Earth would have been greatly influenced by the chemical environment and the thiolate containing scaffold. The discovery that all the major classes of iron-sulfur clusters easily form under prebiotically reasonable conditions broadens the chemistry accessible to protometabolic systems. Show less

Mitochondrial Ca 2+ uptake plays a pivotal role both in cell energy balance and in cell fate determination. Studies on the role of mitochondrial Ca 2+ signaling in pathophysiology have been favored by the identification of the genes encoding the mitochondrial calcium uniporter (MCU) and its regulatory subunits. Thus, research carried on in the last years on one hand has determined the structure of the MCU complex and its regulation, on the other has uncovered the consequences of dysregulated mitochondrial Ca 2+ signaling in cell and tissue homeostasis. Whether mitochondrial Ca 2+ uptake can be exploited as a weapon to counteract cancer progression is debated. In this review, we summarize recent research on the molecular structure of the MCU, the regulatory mechanisms that control its activity and its relevance in pathophysiology, focusing in particular on its role in cancer progression. Show less