Abstract
Organelle intercommunication represents a wide area of interest. Over the last few decades, increasing evidence has highlighted the importance of organelle contact sites in many biological processes including Ca2+ signaling, lipid biosynthesis, apoptosis, and autophagy but also their involvement in pathological conditions. ER–mitochondria tethering is one of the most investigated inter-organelle communications and it is differently modulated in response to several cellular conditions including, but not limited to, starvation, Endoplasmic Reticulum (ER) stress, and mitochondrial shape modifications. Despite many studies aiming to understand their functions and how they are perturbed under different conditions, approaches to assess organelle proximity are still limited. Indeed, better visualization and characterization of contact sites remain a fascinating challenge. The aim of this review is to summarize strengths and weaknesses of the available methods to detect and quantify contact sites, with a main focus on ER–mitochondria tethering.
Highlights
In eukaryotes, organelles are delimited by a membrane that enables them to perform specific and unique tasks, whose characterization has been the goal of researchers for many decades
In addition to Ca2+ signaling, other cellular functions have been linked to MAMs. Even though it is out of the scope of this review to provide an in-depth focus on MAM functions and dysfunctions, we report a general overview since we believe that it is important to understand them in order to better appreciate the reports available that investigate the endoplasmic reticulum (ER)–mitochondria interplay
As reported in the second paragraph, the ER–mitochondria tethering is characterized by four main players, IP3R–GRP75–VDAC [39], B cell receptor-associated protein31 (BAP31)–FIS1 [36], Mfn2 [28], and VAP–protein tyrosine phosphatase-interacting protein-51 (PTPIP51) [32]
Summary
Organelles are delimited by a membrane that enables them to perform specific and unique tasks, whose characterization has been the goal of researchers for many decades. The inter-organelle communication received momentum and represents an emerging aspect in cell biology. It is well established that organelles are not isolated, but they are interconnected, thereby forming a communicating network [1]. Proteins identified at the interface between organelles seem to act as tethers that physically bridge two opposing membranes and join them to each other [2,3]; others have a specific role that occurs at the contact sites, such as the ability to transfer small molecules in a non-vesicular manner [4,5]. The interplay between the endoplasmic reticulum (ER) and mitochondria has been one of the first identified and, to date, still represents one of the best characterized forms. Many shreds of evidence report that its alteration is linked to the development of different disorders including diabetes [14], cancer [15], and neurodegenerative diseases (e.g., Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) [16])
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