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Altered trafficking of miRNAs at mitochondria modulates mitochondrial functions and cell death in brain ischemia.
Free Radic Biol Med. 2023 Apr; 199:26-33.FR

Abstract

Stroke is one of the major causes of death and disabilities worldwide. The rapid induction of cell death by necrosis and apoptosis is observed at the ischemic core, while long lasting apoptosis and brain inflammation continue in the penumbra. The emerging evidence suggests a critical role of mitochondria in acute and chronic inflammation and cell death. Mitochondrial dysfunction may result in the release of mitokines and/or mitochondrial DNA into the cytoplasm and activate multiple cytosolic pathways which in turn triggers inflammation. The role of miRNA, specifically mitochondria-associated miRNAs (mitomiRs) in the regulation of mitochondrial functions is emerging. In the current study, we hypothesized that ischemia-induced mitomiRs may modulate the mitochondrial functions and such alterations under stress conditions may lead to mitochondrial dysfunction and cell death. We have demonstrated the specific pattern of miRNAs associated with mitochondria that is altered under ischemic condition induced by transient middle artery occlusion (tMCAo) in rats. The putative targets of altered miRNAs include several mitochondrial proteins which signifies their involvement in maintaining mitochondrial homeostasis. The alteration of selected miRNAs in mitochondria was further detected in a cellular models when hypoxia was induced using a chemical agent CoCl2, in three cell lines. Two candidate mitomiRs, hsa-miR-149-3p and hsa-miR-204-5p were further analyzed for their functional role during in vitro hypoxia by transfecting mitomiR mimics into cells and determining critical mitochondrial functions and cell viability. The results here emphasize the role of certain mitomiRs as an important modulator of mitochondrial function under the ischemic condition.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Gohel D
Department of Biochemistry, Faculty of Science, The M.S. University of Baroda, Vadodara, 390002, Gujarat, India; Department of Genomic Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
Shukla S
Department of Biochemistry, Faculty of Science, The M.S. University of Baroda, Vadodara, 390002, Gujarat, India.
Rajan WD
Laboratory of Molecular Neurobiology, The Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093, Warsaw, Poland.
Wojtas B
Laboratory of Molecular Neurobiology, The Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093, Warsaw, Poland.
Kaminska B
Laboratory of Molecular Neurobiology, The Nencki Institute of Experimental Biology of the Polish Academy of Sciences, 02-093, Warsaw, Poland. Electronic address: b.kaminska@nencki.edu.pl.
Singh R
Department of Biochemistry, Faculty of Science, The M.S. University of Baroda, Vadodara, 390002, Gujarat, India; Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, 221005, India. Electronic address: singhraj1975@gmail.com.

MeSH

RatsAnimalsMicroRNAsMitochondriaApoptosisBrain IschemiaInflammationHypoxia

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

36781060

Citation

Gohel, Dhruv, et al. "Altered Trafficking of miRNAs at Mitochondria Modulates Mitochondrial Functions and Cell Death in Brain Ischemia." Free Radical Biology & Medicine, vol. 199, 2023, pp. 26-33.
Gohel D, Shukla S, Rajan WD, et al. Altered trafficking of miRNAs at mitochondria modulates mitochondrial functions and cell death in brain ischemia. Free Radic Biol Med. 2023;199:26-33.
Gohel, D., Shukla, S., Rajan, W. D., Wojtas, B., Kaminska, B., & Singh, R. (2023). Altered trafficking of miRNAs at mitochondria modulates mitochondrial functions and cell death in brain ischemia. Free Radical Biology & Medicine, 199, 26-33. https://doi.org/10.1016/j.freeradbiomed.2023.02.004
Gohel D, et al. Altered Trafficking of miRNAs at Mitochondria Modulates Mitochondrial Functions and Cell Death in Brain Ischemia. Free Radic Biol Med. 2023;199:26-33. PubMed PMID: 36781060.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Altered trafficking of miRNAs at mitochondria modulates mitochondrial functions and cell death in brain ischemia. AU - Gohel,Dhruv, AU - Shukla,Shatakshi, AU - Rajan,Wenson David, AU - Wojtas,Bartosz, AU - Kaminska,Bozena, AU - Singh,Rajesh, Y1 - 2023/02/11/ PY - 2022/12/17/received PY - 2023/1/31/revised PY - 2023/2/7/accepted PY - 2023/2/14/pubmed PY - 2023/3/21/medline PY - 2023/2/13/entrez KW - Brain ischemia KW - CoCl(2) KW - HIF-1α KW - Mitochondria KW - miRNAs KW - mitomiRs SP - 26 EP - 33 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 199 N2 - Stroke is one of the major causes of death and disabilities worldwide. The rapid induction of cell death by necrosis and apoptosis is observed at the ischemic core, while long lasting apoptosis and brain inflammation continue in the penumbra. The emerging evidence suggests a critical role of mitochondria in acute and chronic inflammation and cell death. Mitochondrial dysfunction may result in the release of mitokines and/or mitochondrial DNA into the cytoplasm and activate multiple cytosolic pathways which in turn triggers inflammation. The role of miRNA, specifically mitochondria-associated miRNAs (mitomiRs) in the regulation of mitochondrial functions is emerging. In the current study, we hypothesized that ischemia-induced mitomiRs may modulate the mitochondrial functions and such alterations under stress conditions may lead to mitochondrial dysfunction and cell death. We have demonstrated the specific pattern of miRNAs associated with mitochondria that is altered under ischemic condition induced by transient middle artery occlusion (tMCAo) in rats. The putative targets of altered miRNAs include several mitochondrial proteins which signifies their involvement in maintaining mitochondrial homeostasis. The alteration of selected miRNAs in mitochondria was further detected in a cellular models when hypoxia was induced using a chemical agent CoCl2, in three cell lines. Two candidate mitomiRs, hsa-miR-149-3p and hsa-miR-204-5p were further analyzed for their functional role during in vitro hypoxia by transfecting mitomiR mimics into cells and determining critical mitochondrial functions and cell viability. The results here emphasize the role of certain mitomiRs as an important modulator of mitochondrial function under the ischemic condition. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/36781060/Altered_trafficking_of_miRNAs_at_mitochondria_modulates_mitochondrial_functions_and_cell_death_in_brain_ischemia_ DB - PRIME DP - Unbound Medicine ER -