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Mitochondria-Endoplasmic Reticulum Contact Sites (MERCS): A New Axis in Neuronal Degeneration and Regeneration

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Abstract

Mitochondria-Endoplasmic Reticulum Contact Sites (MERCS) are dynamic structures whose physiological interaction is vital to direct life and death of the cell. A bevy of tethering proteins, mitofusin-1/2 (Mfn-1/2), glucose-regulated protein-75 (Grp-75), voltage-dependent anion channel-1 (VDAC1), and dynamic-related protein-1 (Drp1), plays an integral role in establishing and regulating this intricate intracellular communication. Dysregulation of this interplay leads to various neurodegenerative disorders, like Alzheimer’s disease (AD), Parkinson’s disease (PD), stroke, traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Although there is an absence of a well-defined molecular background that dictates the pathway of MERCS, adequate exploration has resulted in preliminary data that suggests its cardinal role in neuroregeneration. The juxtaposition of mitochondria and ER has a critical function in cell senescence, thus regulating regeneration. Axonal regeneration and brain tissue regeneration, using reactive astrocytes, are studied most extensively. Overexpression of Grp-75 promoted axonal regeneration post a nerve injury. Attempts have been made to exploit MERCS as potential therapeutic drug targets for enhancing neuroregeneration and impeding neurodegeneration. Novel strategies have been developed to aid the delivery of mitochondria into the neuronal cell body, which in turn establishes a network with the presiding ER resulting in contact site formation. The fascinating aspect of this mechanism is that despite the lack of inherent regenerative capacity in neurons, it can be induced by modifying MERCS.

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Author notes

  1. Vijaya Harini Sathyamurthy and Yoghalakshmi Nagarajan contributed equally to this work.

Authors and Affiliations

  1. Department of Biomedical Sciences, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, 600116, India

    Vijaya Harini Sathyamurthy, Yoghalakshmi Nagarajan & Venkatachalam Deepa Parvathi

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  1. Vijaya Harini Sathyamurthy
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Contributions

Vijaya Harini Sathyamurthy, Yoghalakshmi Nagarajan and Venkatachalam Deepa Parvathi contributed to the concept, review of literature and manuscript preparation. Vijaya Harini Sathyamurthy and Yoghalakshmi Nagarajan contributed equally towards the draft and figures. Venkatachalam Deepa Parvathi supervised the research work and finalised (review and editing) the manuscript.

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Correspondence to Venkatachalam Deepa Parvathi.

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Sathyamurthy, V.H., Nagarajan, Y. & Parvathi, V.D. Mitochondria-Endoplasmic Reticulum Contact Sites (MERCS): A New Axis in Neuronal Degeneration and Regeneration. Mol Neurobiol (2024). https://doi.org/10.1007/s12035-024-03971-6

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