PIF2024 - CI4Health: Biogenetic regulation of human mitochondrial respiratory chain complex I in health and disease (PID2023-147288NB-I00)

CI4Health operates within the framework of non-oriented projects in Biomedicine, focusing on advancing crucial insights into the fundamental molecular bases of mitochondrial diseases (MDs). These disorders arise from functional disruptions in the mitochondrial respiratory chain (MRC) complexes, and constitute the primary cause of inborn errors in energy metabolism. Among them, isolated complex I (CI) enzyme deficiency (MIM#252010) stands out as the most prevalent cause (>30%) of MDs. Despite broad information of its molecular genetic origins, no therapy currently exists for the affected patients due to limited knowledge on its pathophysiology. Our overarching objective is to achieve a comprehensive understanding of the molecular mechanisms governing the biogenesis and functionality of CI and its components, and how CI deficiency impacts on the overall function of the MRC. CI4Health expands on the previous basic research conducted by our research team to delve into novel molecular mechanisms in CI pathophysiology. This will yield pioneering contributions by leveraging its interdisciplinary approach, merging the areas of Genetics, Biochemistry, Cellular, Molecular and Structural Biology. The insights gained will serve as a crucial foundation for developing therapeutic interventions to address CI-related disorders and, more generally, MDs.