Reduction of ER-Mitochondria Distance: a Key Feature in Alzheimer's and Parkinson's Disease, and During Cancer Treatment.

One remarkable dynamic cell structure is the region between the endoplasmic reticulum (ER) and the mitochondria, termed the mitochondria-associated membranes (MAM). MAMs carry out different cellular functions such as Ca homeostasis and lipid synthesis, which depend on an adequate distance separating the ER and mitochondria. A decreased distance has been observed in Alzheimer's disease, Parkinson's disease, and during cancer treatment. It is unclear how dysregulation of the spatial characteristics of MAMs can cause abnormal Ca dynamics which could end in cell death. In this work, a computational model was proposed to study the relationship between a decreased ER-mitochondria distance and mitochondria-induced cell death. Our results point towards the mitochondrial permeability transition pore (mPTP) as a key cell death signaling mechanism indirectly regulated by the spatial characteristics of MAMs.Clinical Relevance- The endoplasmic reticulum-mitochondria crosstalk plays an important role in the mPTP-induced apoptosis. This process could be behind neurodegeneration in Alzheimer's and Parkinson's diseases, as well as behind the induced cell death during cancer treatment.