Mitochondria-associated membranes (MAMs) are subdomains of the endoplasmic reticulum (ER) that have been suggested to interact with mitochondria. This membrane scrambling between ER and mitochondria appears to play a critical role in the earliest steps of autophagy. Moreover, lipid microdomains, i.e. lipid rafts, have been identified as further actors of the autophagic process. Autophagy is a ubiquitous intracellular degradation pathway, whose levels need to be tightly controlled to secure cell homeostasis. In fact, this process acts at basal levels to maintain a continuous and effective intracellular clearance but it may also be induced in a number of stress conditions. It has been hypothesized that alteration in MAM's function leads to majority of human disorders, and in particular can contribute to the loss of neural function and potentially to the cell death associated with neurodegeneration.
Thus, this research program is divided into 4 main objectives:
1. Evaluation of raft-like microdomains in the regulation of autophagy.
2. Analysis of a possible implication of MAM raft-like microdomains during early steps of autophagosome generation.
3. Proteomic analysis of MAMs in the absence or following autophagic stimulus.
4. Analysis of a possible role of autophagy on neuroprotection through MAM raft-like microdomains in neuroblastoma cells.
