Peroxisomal lipid and ROS signaling in mammalian cells.

Peroxisomes are multifunctional cell organelles that play an important role in the metabolism of lipids and reactive oxygen species (ROS). Over the years, a considerable amount of evidence has been collected that disturbances in peroxisomal metabolism can have significant consequences for human health. However, at present, it is still unclear the extent to which defects in peroxisomal metabolism lead to cellular and organismal pathologies. A hypothesis gaining prominence is that low concentrations of peroxisomal ROS can exert important physiological roles in cellular signaling and proliferation, and that a disturbance of peroxisomal metabolism may trigger signaling/communication events that ultimately result in increased mitochondrial stress and the activation of mitochondrial stress pathways. This research project is intended to further our understanding of how peroxisomal metabolism can evoke cytoprotective actions or initiate signaling cascades involved in pathophysiological responses. Specifically, we will (i) study the link between peroxisomal (dys)function and cellular oxidative stress, (ii) inventorize the proximal targets for peroxisomal ROS, (iii) investigate the molecular mechanisms underlying the stress-related communication events between peroxisomes and mitochondria, and (iv) analyze the novel identified targets and mechanisms in tissues from mice suffering from peroxisome-dependent and oxidative stress-related diseases. The outcome of this research is particularly relevant to understanding the consequences of demise of peroxisome function which accompanies cellular senescence, organismal aging, and age-related diseases.

Keywords:Oxidative stress-related disorders, Organelle contact sites, Peroxisome biogenesis disorders, Lipid signaling, Protein disulfide signaling, Redox signaling, Mitochondria, Peroxisomes

Disciplines:Other biological sciences, Laboratory medicine, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences