During the past years, our research has been focused on understanding how mitochondrial energy metabolism contributes to the integration of cellular functions, leading to the onset and progression of various pathologies. Complex regulatory mechanisms enable mitochondrial metabolism to meet cellular demands, which go beyond ATP production. We have demonstrated that mitochondrial oxidative phosphorylation also plays additional roles in controlling cell immunity and inflammation (Formentini L. et al., Cell Reports, 2017, PMID: 28494869) and regulating intra- and inter-cellular oncogenic signals (Nuevo-Tapioles, C. et al., Nature Communications, 2020, PMID: 32681016). Impaired mitochondrial function also significantly affects adipose tissue and skeletal muscle lipid species and metabolism (Formentini L et al., Diabetologia, 2017, PMID: 28770317; Sanchez-Gonzalez C et al, EMBO J. 2020, PMID: 32488939). Interestingly, these metabolic disturbances impair ROS and calcium signaling, leading to profound changes in muscle structure (Sanchez-Gonzalez C et al, Cell Death and Disease 2022, PMID: 32488939), thus emerging as key hallmarks of myopathies. Very recently, we have demonstrated the existence of a metabolon in skeletal muscle, aimed at integrating nutrient catabolism with mitochondrial efficiency (Nat Metabolism 2024, doi: 10.1038/s42255-023-00956-y).

Current Aims

One of the main goals of my research line, supported by PID2022-136738OB-I00 national funding and Fundación Ramón Areces, is to further investigate mitochondrial metabolism in pathophysiology. Using two conditional and tissue-specific mouse models with impaired mitochondrial activity (dysfunctional oxidative phosphorylation mice, LowOXPHOS mice; dysfunctional fatty acid oxidation mice, LowFAO mice), our research group is elucidating how different mitochondrial dysfunctions, environmental factors, and diets impact metabolism at the cellular, tissue, and organismal levels. We aim to identify the aspects of mitochondrial activity that limit cell homeostasis and understand which products of metabolism are essential for proper organism function, as well as how cells obtain or transform them in physiological tissue environments. This knowledge is crucial for exploiting mitochondrial metabolism for therapeutic purposes in the field of cancer and ageing.