Mind the Gap: Mitochondria and the Endoplasmic Reticulum in Neurodegenerative Diseases

The way organelles are viewed by cell biologists is quickly changing. For many years, these cellular entities were thought to be unique and singular structures that performed specific roles. However, in recent decades, researchers have discovered that organelles are dynamic and form physical contacts. In addition, organelle interactions modulate several vital biological functions, and the dysregulation of these contacts is involved in cell dysfunction and different pathologies, including neurodegenerative diseases. Mitochondria-ER contact sites (MERCS) are among the most extensively studied and understood juxtapositioned interorganelle structures. In this review, we summarise the major biological and ultrastructural dysfunctions of MERCS in neurodegeneration, with a particular focus on Alzheimer's disease as well as Parkinson's disease, amyotrophic lateral sclerosis and frontotemporal dementia. We also propose an updated version of the MERCS hypothesis in Alzheimer's disease based on new findings. Finally, we discuss the possibility of MERCS being used as possible drug targets to halt cell death and neurodegeneration.

Automated summary

The view of organelles by cell biologists is changing rapidly, as they are now recognized as dynamic structures that form physical contacts and modulate important biological functions. Dysregulation of these contacts may lead to various pathologies. Mitochondria-ER contact sites (MERCS) are extensively studied interorganelle structures, particularly in neurodegenerative diseases like Alzheimer's and Parkinson's. MERCS could potentially be used as drug targets to prevent cell death and neurodegeneration.