Abstract
Contact sites between mitochondria and endoplasmic reticulum (ER) are points in which the two organelles are in close proximity. Due to their structural and functional complexity, their exploitation as pharmacological targets has never been considered so far. Notwithstanding, the number of compounds described to target proteins residing at these interfaces either directly or indirectly is rising. Here we provide original insight into mitochondria–ER contact sites (MERCs), with a comprehensive overview of the current MERCs pharmacology. Importantly, we discuss the considerable potential of MERCs to become a druggable target for the development of novel therapeutic strategies.
Highlights
Mitochondria–endoplasmic reticulum contact sites (MERCs) have been so far the primary actor in the scene of organelle contact sites
A full description of mitochondria–ER contact sites (MERCs) composition, structure, and functions is beyond the scope of this review, and it has been covered by previously published articles, so we refer the reader to the appropriate literature [1–3]
As happens in many biological systems, structural parameters have an impact on MERCs functions; we have recently proposed that MERCs function could be dual, that is, “vertical” or “horizontal” [6]
Summary
Mitochondria–endoplasmic reticulum contact sites (MERCs) have been so far the primary actor in the scene of organelle contact sites. (MFN2) is fundamental in shaping the job of pro-opiomelanocortin (POMC) neurons and its ablation leads to leptin resistance and whole-body energy imbalance [4] This effect is linked to the tethering function of MFN2 at MERCs, MFN2 possesses other subcellular tasks such as participation in the mitochondrial fusion process. The second term refers to the activity of enzymes located at MERCs interfaces that account for the quantity of molecules here produced or processed, as in the case of cholesteryl esters [7] This “structure and function relationship” has not yet been clarified, but future studies are guaranteed. Because of these structural features and their pleiotropic nature, MERCs (and more in general all membrane contact sites) appear as a highly complex system and a difficult target for drug discovery. We speculate on the possibility that chemical modulators of organelle contact sites are the frontier in pharmacology—in this context, not a single molecule but a whole set of juxtaposing membranes (composed of specific subsets of lipids and proteins) will be exploited as a novel druggable target
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