Membrane Homeostasis Affectations

Our research line is focus on the alterations in lipid metabolism associated to T2D. In this regard, there is clinical evidence for the association between phospholipids (PL) membranes composition and insulin sensitivity. Metabolomic analysis of newly developed type 2 diabetics versus normoglycemic subjects suggested that an abnormal composition of phosphatidylcholine (PC) may contribute to develop insulin resistance. Besides, alterations in mitochondrial dynamics, defined as the processes of mitochondrial fusion and fission, have been observed in T2D. The main proteins involved in mitochondrial fusion are Mitofusins (Mfn1 and Mfn2) and Optic atrophy 1 (OPA1). There are evidence connecting the loss of mitochondrial fusion proteins with defects in insulin sensitivity. In this sense, a deficiency in Mfn2, a protein that tethers endoplasmic reticulum (ER) to mitochondria, causes a reduction in PC synthesis, leading to ER stress and insulin resistance in the liver. Our aim is to demonstrate that mitochondrial fusion proteins are involved in the intracellular phospholipid homeostasis, and in turn, to search for a novel therapeutic target for chronic diseases associated to insulin resistance.