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 Ca2+ 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 Ca2+ 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.