POTENTIAL MITOCHONDRIAL REGULATORS: FUNCTIONAL VALIDATION BY INTEGRATED APPROACHES

As sites of the main oxidative reactions and of the electron transport chain, mitochondria are the organelle committed to metabolic energy production required for all cellular functions. Because of their ubiquitous presence, mitochondrial density and function have a significant impact on whole-body metabolism. Many aspects at the basis of mitochondrial regulation have not been fully deciphered; hence, finding new mitochondrial regulators is a major challenge, both for basic science and for translational medicine. Integrating different approaches like high-throughput screening, staining assays, bioinformatics tools and biochemical and functional approaches, we were able starting from 27000 cDNAs to identify one new mitochondrial regulator, Zc3h10, whose metabolic function was previously completely unknown. The overexpression of this gene increases both the mitochondrial biogenesis and activity, at levels comparable to those observed in cells overexpressing PGC-1α, a very well known mitochondrial regulator, Notably, Zc3h10 increased mitochondrial respiration, without affecting ROS production or apoptosis. In addition, in mice Zc3h10 is expressed in different tissues, especially those characterized by high mitochondria content. Although the precise molecular mechanism by which Zc3h10 regulates mitochondria needs to be investigated in more detail, the findings reported in this thesis help to gain new insights on the biology of mitochondria.