The Mitochondria-Associated ER Membranes Are Novel Subcellular Locations Enriched for Inflammatory-Responsive MicroRNAs

Wang Xia Wang, Paresh Prajapati, Peter T. Nelson, Joe E. Springer

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) are specific ER domains that contact the mitochondria and function to facilitate communication between ER and mitochondria. Disruption of contact between the mitochondria and ER is associated with a variety of pathophysiological conditions including neurodegenerative diseases. Considering the many cellular functions of MAMs, we hypothesized that MAMs play an important role in regulating microRNA (miRNA) activity linked to its unique location between mitochondria and ER. Here we present new findings from human and rat brains indicating that the MAMs are subcellular sites enriched for specific miRNAs. We employed subcellular fractionation and TaqMan® RT-qPCR miRNA analysis to quantify miRNA levels in subcellular fractions isolated from male rat brains and six human brain samples. We found that MAMs contain a substantial number of miRNAs and the profile differs significantly from that of cytosolic, mitochondria, or ER. Interestingly, MAMs are particularly enriched in inflammatory-responsive miRNAs, including miR-146a, miR-142-3p, and miR-142-5p in both human and rat brains; miR-223 MAM enrichment was observed only in human brain samples. Further, mitochondrial uncoupling or traumatic brain injury in male rats resulted in the alteration of inflammatory miRNA enrichment in the isolated subcellular fractions. These observations demonstrate that miRNAs are distributed differentially in organelles and may re-distribute between organelles and the cytosol in response to cellular stress and metabolic demands.

Original languageEnglish
Pages (from-to)2996-3013
Number of pages18
JournalMolecular Neurobiology
Volume57
Issue number7
DOIs
StatePublished - Jul 1 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

Funding

Sincere thanks are given to the research volunteers at the Alzheimer’s Disease Center at the University of Kentucky (UK-ADC), supported by NIH grant P30 AG280303. This work was supported by a grant from the Kentucky Spinal Cord and Head Injury Research Trust (KSCHIRT 15-12A and 18 8A) and a KSCHIRT endowment Acknowledgments

FundersFunder number
UK-ADC
National Institutes of Health (NIH)P30 AG280303
National Institutes of Health (NIH)
University of Kentucky
Kentucky Spinal Cord and Head Injury Research TrustKSCHIRT 15-12A, 18 8A
Kentucky Spinal Cord and Head Injury Research Trust

    Keywords

    • Mitochondria-associated ER membrane
    • Neurodegeneration
    • Subcellular
    • Traumatic brain injury
    • miR-146a
    • microRNA

    ASJC Scopus subject areas

    • Neurology
    • Cellular and Molecular Neuroscience
    • Neuroscience (miscellaneous)

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