Mitochondria are critical organelles in the context of cell physiology. Mitochondria are the cell energy powerplants by producing the majority of the chemical energy, and play an important role in cell death and quality control processes. Since mitochondria are also active players in cellular redox and calcium homeostasis, as well as in intermediate metabolism, the general objective of our research group is to provide insights into the role of mitochondrial alterations in metabolism, redox signaling and stress responses in chemical toxicology, cancer, cardiovascular and hepatic diseases, aging, and stem cell differentiation.

Our group is particularly interested in finding out whether intrinsic, pharmacological or non-pharmacological (e.g. by exercise) regulation of mitochondrial biogenesis/metabolism and quality control alters (cancer) reduces organ injury during distinct pathologies or as caused by the toxicity of different xenobiotics. The mechanisms of mitochondrial biogenesis and regulation by molecules such as resveratrol or proteins such as sirtuins are important scientific questions. In the same context, another important aim is to investigate how regulation of mitochondrial activity impacts (cancer) stem cell differentiation.

Different molecules or pathologies activate mitochondrial stress/toxicity responses, affecting the cell phenotype and often organ survival. Among the different xenobiotics tested by our research group in the context of mitochondrial toxicology, we highlight anti-cancer agents such as anthracyclines, anti-estrogens or retinoids. Similarly, we developed a library of distinct mitochondrial-directed molecules to investigate their potential as future anti-neoplastic or antioxidant agents. In the framework of mitochondrial alterations during the aging process, another objective of our group is to investigate the role of bone mitochondrial bioenergetics impairment and mitochondrial/peroxisomal fatty acid beta-oxidation unbalance on estrogen-deprivation-induced menopause.

A metabolic approach to some of the biological problems described above has been performed in collaboration with other CNC researchers through the use of nuclear magnetic resonance (NMR)-based metabolomics, which allows for a precise fingerprinting of metabolite fluxes in each condition. Our objective is to use this approach to couple mitochondrial alterations to overall cell metabolism in the context of disease and toxicology.

Research Lines

• Mitochondrial Toxicology and Experimental Therapeutics
  (P.I. Paulo Oliveira)

• Menopause, Aging and Metabolism
  (P.I. Vilma Sardão)

• Mitochondrial Signaling and Metabolic Dysfunction
  (P.I. Anabela Rolo, Carlos Palmeira)