Abstract
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.
Highlights
The way organelles are viewed by cell biologists is quickly changing
We aimed to summarize the role of Mitochondria–endoplasmic reticulum (ER) contact sites (MERCS) in some of the most common
In Alzheimer’s disease (AD), most of the published reports point out that the connectivity between the ER and mitochondria is upregulated, leading to alterations in functions related to MERCS, including Ca2+ shuttling from the ER to mitochondria, autophagosome formation and amyloid β-peptide (Aβ) formation
Summary
The Earth is 4.5 billion years old, and life on our planet began approximately 3.8 billion years ago. Pre-eukaryotic cells originated between approximately one and two billion years after the first cells emerged upon the engulfment of a facultative anaerobe, α-proteobacterium, by an archaebacterium, developing an endosymbiotic relationship and allowing them to evolve together [2,4] This symbiosis provided several advantages over other cells. The engulfed α-proteobacterium could convert oxygen into energy, which allowed a sixfold increase in energy production upon glucose degradation in the new pre-eukaryotic cell, which conferred a competitive advantage over other organisms [5]. This endosymbiotic relationship led to the precursor of eukaryotic cells as we know them today, with α-proteobacteria being the precursors of mitochondria. We provide an updated overview of the relevant molecular composition and the dysregulated MERCS-related biological pathways in Alzheimer’s disease (AD), with a brief overview of these factors in Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD)
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