The long-term research interest of our laboratory is to understand the mechanisms that drive mitochondria to dysfunction and failure in neurodegenerative diseases (such as Alzheimer’s Disease and Parkinson’s Disease), as well as in neuronal aging. By understanding these mechanisms, we will be able to propose new pharmacological targets to prevent, counteract or reverse the cellular damage and the increased levels of apoptotic cell death associated with mitochondrial dysfunction and failure in these conditions.

Our laboratory focuses its efforts on understanding the role of mitochondrial inorganic polyphosphate (polyP) in mitochondrial physiology. PolyP is a molecule that is well-conserved throughout evolution. Composed of multiple subunits of orthophosphate that are linked together by high-energy phosphoanhydride bonds, this polymer is present in numerous tissues of organisms that have been studied. PolyP shows a ubiquitous distribution, though we have observed a preference for co-localization with mitochondria, in mammalian cells.   Interestingly, in 1999, the Nobel Laureate Arthur Kornberg and his colleagues reported that bacteria with decreased levels of polyP are hypersensitive to a variety of stressors. Corroborating this data, other researchers have proposed the role of polyP in the cellular protection against increased oxidative stress, and protein dyshomeostasis. Moreover, the participation of polyP on the regulation of mitochondrial calcium homeostasis and apoptosis has also been proven.

By using mammalian models combined with microscopy, cell biology, molecular biology, protein biology, and biophysics techniques, our aim is to understand the key contribution of polyP towards mitochondrial physiology and dysfunction in neurodegeneration and aging. Specifically, we are interested in the study of the role of polyP and the molecular mechanisms of its effects in the following physiological processes, all of them altered in neurodegeneration and neuronal aging:

  1. Mitochondrial protein homeostasis (including the mitochondrial unfolded protein response, UPRmt and its relationship with mitophagy)
  2. Mitochondrial dynamics, mitophagy and apoptosis.
  3. Mitochondrial bioenergetics and oxidative stress response (including OXPHOS and glycolysis and the Glutathione and SIRT3 pathways)

Moreover, we are open to collaborate with other groups with different interests. Currently, in collaboration with other groups, we are conducting studies on the role of smallRNAs in mitochondria in Alzheimer’s disease and in growing synthetic materials in mammalian cells.