ArticleCirculation research2012
Nuclear miRNA regulates the mitochondrial genome in the heart.
Article in Circulation research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers, 1 of them a synthesis that pooled it.
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Who cites it
190 citing papers in PubMed, 1 synthesis or guideline pooled it, 352 citations in OpenAlex.
- The expression profiles and roles of microRNAs in cardiac glucose metabolism.Frontiers in endocrinology · 2025Pooled it
- Fraction-Seq: An Integrated Experimental and Computational Workflow for Determining the Localization and Abundance of Small Non-Coding RNAs in Subcellular Compartments.Non-coding RNA · 2026Article
- Mitochondrial translational control in cardiovascular diseases: from mechanisms to therapies.Redox biology · 2026Review
- A Distinct Population of Mitochondrial miRNA in Human Male Skeletal Muscle Assessed Before and After Exercise.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Mitochondrial miRNA- miR-181c-5p and mitomiR-106a-5p levels as indicators in cardiovascular disease patients.Molecular biology reports · 2026Article
- Advances in mitochondria-nucleus crosstalk in septic cardiomyopathy.Cell biology and toxicology · 2025Review
- Mechanisms of microRNA trafficking to mitochondria in the heart.Current opinion in physiology · 2025Article
- Exosome-Mediated Mitochondrial Delivery of Antisense Oligonucleotides.Nucleic acid therapeutics · 2025Article
- The emerging role of miRNAs in biological aging and age-related diseases.Non-coding RNA research · 2025Review
- The roles of subcellular Argonaute 2 in cardiovascular diseases.Journal of translational internal medicine · 2025Article
- Skeletal Muscle Mitochondria Contain Nuclear-Encoded RNA Species Prior to and Following Adaptation to Exercise Training in Rats.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Induction of mitochondrial damage via the CREB3L1/miR-34c/COX1 axis by porcine epidemic diarrhea virus infection facilitates pathogenicity.Journal of virology · 2025Article
- Extracellular microvesicles/exosomes-magic bullets in horizontal transfer between cells of mitochondria and molecules regulating mitochondria activity.Stem cells (Dayton, Ohio) · 2025Review
- Review
- Mitochondrial microRNAs: Key Drivers in Unraveling Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Mitochondria-associated non-coding RNAs and their impact on drug resistance.Frontiers in pharmacology · 2025Review
- Effect of Mesenchymal Stem Cell-Derived Extracellular Vesicles Induced by Advanced Glycation End Products on Energy Metabolism in Vascular Endothelial Cells.Kidney international reports · 2025Article
- Mitochondrial RNA in Inflammation.International journal of biological sciences · 2025Review
- Purification of mitochondria from skeletal muscle tissue for transcriptomic analyses reveals localization of nuclear-encoded noncoding RNAs.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the Whole.Antioxidants (Basel, Switzerland) · 2024Review
130 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleMitochondria are semiautonomous cellular organelles with their own genome, which not only supply energy but also participate in cell death pathways. MicroRNAs (miRNAs) are usually 19 to 25 nt long, noncoding RNAs, involved in posttranscriptional gene regulation by binding to the 3'-untranslated regions of target mRNA, which impact on diverse cellular processes.
objectiveTo determine if nuclear miRNAs translocate into the mitochondria and regulate mitochondrial function with possible pathophysiological implications in cardiac myocytes. METHODS AND
resultsWe find that miR-181c is encoded in the nucleus, assembled in the cytoplasm, and finally translocated into the mitochondria of cardiac myocytes. Immunoprecipitation of Argonaute 2 from the mitochondrial fraction indicates binding of cytochrome c oxidase subunit 1 (mt-COX1) mRNA from the mitochondrial genome with miR-181c. Also, a luciferase reporter construct shows that mi-181c binds to the 3'UTR of mt-COX1. To study whether miR-181c regulates mt-COX1, we overexpressed precursor miR-181c (or a scrambled sequence) in primary cultures of neonatal rat ventricular myocytes. Overexpression of miR-181c did not change mt-COX1 mRNA but significantly decreased mt-COX1 protein, suggesting that miR-181c is primarily a translational regulator of mt-COX1. In addition to altering mt-COX1, overexpression of miR-181c results in increased mt-COX2 mRNA and protein content, with an increase in both mitochondrial respiration and reactive oxygen species generation in neonatal rat ventricular myocytes. Thus, our data show for the first time that miR-181c can enter and target the mitochondrial genome, ultimately causing electron transport chain complex IV remodeling and mitochondrial dysfunction.
conclusionsNuclear miR-181c translocates into the mitochondria and regulates mitochondrial genome expression. This unique observation may open a new dimension to our understanding of mitochondrial dynamics and the role of miRNA in mitochondrial dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.