MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes
Metabolic syndrome increases the risk for cardiovascular disease including metabolic cardiomyopathy that may progress to heart failure. The decline in mitochondrial metabolism is considered a critical pathogenic mechanism that drives this progression. Considering its cardiac specificity, we hypothes...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/10/11/3152 |
| _version_ | 1797510831255060480 |
|---|---|
| author | Naveen Mekala Jacob Kurdys Alexis Paige Vicenzi Leana Rose Weiler Carmen Avramut Edwin J. Vazquez Neli Ragina Mariana G. Rosca |
| author_facet | Naveen Mekala Jacob Kurdys Alexis Paige Vicenzi Leana Rose Weiler Carmen Avramut Edwin J. Vazquez Neli Ragina Mariana G. Rosca |
| author_sort | Naveen Mekala |
| collection | DOAJ |
| description | Metabolic syndrome increases the risk for cardiovascular disease including metabolic cardiomyopathy that may progress to heart failure. The decline in mitochondrial metabolism is considered a critical pathogenic mechanism that drives this progression. Considering its cardiac specificity, we hypothesized that miR 208a regulates the bioenergetic metabolism in human cardiomyocytes exposed to metabolic challenges. We screened in silico for potential miR 208a targets focusing on mitochondrial outcomes, and we found that mRNA species for mediator complex subunit 7, mitochondrial ribosomal protein 28, stanniocalcin 1, and Sortin nexin 10 are rescued by the CRISPR deletion of miR 208a in human SV40 cardiomyocytes exposed to metabolic challenges (high glucose and high albumin-bound palmitate). These mRNAs translate into proteins that are involved in nuclear transcription, mitochondrial translation, mitochondrial integrity, and protein trafficking. MiR 208a suppression prevented the decrease in myosin heavy chain α isoform induced by the metabolic stress suggesting protection against a decrease in cardiac contractility. MiR 208a deficiency opposed the decrease in the mitochondrial biogenesis signaling pathway, mtDNA, mitochondrial markers, and respiratory properties induced by metabolic challenges. The benefit of miR 208a suppression on mitochondrial function was canceled by the reinsertion of miR 208a. In summary, miR 208a regulates mitochondrial biogenesis and function in cardiomyocytes exposed to diabetic conditions. MiR 208a may be a therapeutic target to promote mitochondrial biogenesis in chronic diseases associated with mitochondrial defects. |
| first_indexed | 2024-03-10T05:36:53Z |
| format | Article |
| id | doaj.art-f1f92ff0eb804f2db78f178c44600698 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:36:53Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-f1f92ff0eb804f2db78f178c446006982023-11-22T22:52:02ZengMDPI AGCells2073-44092021-11-011011315210.3390/cells10113152MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged CardiomyocytesNaveen Mekala0Jacob Kurdys1Alexis Paige Vicenzi2Leana Rose Weiler3Carmen Avramut4Edwin J. Vazquez5Neli Ragina6Mariana G. Rosca7Department of Foundational Sciences, Central Michigan University College of Medicine, Mount Pleasant, MI 48858, USADepartment of Foundational Sciences, Central Michigan University College of Medicine, Mount Pleasant, MI 48858, USADepartment of Foundational Sciences, Central Michigan University College of Medicine, Mount Pleasant, MI 48858, USADepartment of Foundational Sciences, Central Michigan University College of Medicine, Mount Pleasant, MI 48858, USADepartment of Foundational Sciences, Central Michigan University College of Medicine, Mount Pleasant, MI 48858, USADepartment of Foundational Sciences, Central Michigan University College of Medicine, Mount Pleasant, MI 48858, USADepartment of Foundational Sciences, Central Michigan University College of Medicine, Mount Pleasant, MI 48858, USADepartment of Foundational Sciences, Central Michigan University College of Medicine, Mount Pleasant, MI 48858, USAMetabolic syndrome increases the risk for cardiovascular disease including metabolic cardiomyopathy that may progress to heart failure. The decline in mitochondrial metabolism is considered a critical pathogenic mechanism that drives this progression. Considering its cardiac specificity, we hypothesized that miR 208a regulates the bioenergetic metabolism in human cardiomyocytes exposed to metabolic challenges. We screened in silico for potential miR 208a targets focusing on mitochondrial outcomes, and we found that mRNA species for mediator complex subunit 7, mitochondrial ribosomal protein 28, stanniocalcin 1, and Sortin nexin 10 are rescued by the CRISPR deletion of miR 208a in human SV40 cardiomyocytes exposed to metabolic challenges (high glucose and high albumin-bound palmitate). These mRNAs translate into proteins that are involved in nuclear transcription, mitochondrial translation, mitochondrial integrity, and protein trafficking. MiR 208a suppression prevented the decrease in myosin heavy chain α isoform induced by the metabolic stress suggesting protection against a decrease in cardiac contractility. MiR 208a deficiency opposed the decrease in the mitochondrial biogenesis signaling pathway, mtDNA, mitochondrial markers, and respiratory properties induced by metabolic challenges. The benefit of miR 208a suppression on mitochondrial function was canceled by the reinsertion of miR 208a. In summary, miR 208a regulates mitochondrial biogenesis and function in cardiomyocytes exposed to diabetic conditions. MiR 208a may be a therapeutic target to promote mitochondrial biogenesis in chronic diseases associated with mitochondrial defects.https://www.mdpi.com/2073-4409/10/11/3152cardiomyocytesmetabolic syndromemiR 208amitochondrial biogenesisbioenergetics |
| spellingShingle | Naveen Mekala Jacob Kurdys Alexis Paige Vicenzi Leana Rose Weiler Carmen Avramut Edwin J. Vazquez Neli Ragina Mariana G. Rosca MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes Cells cardiomyocytes metabolic syndrome miR 208a mitochondrial biogenesis bioenergetics |
| title | MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes |
| title_full | MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes |
| title_fullStr | MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes |
| title_full_unstemmed | MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes |
| title_short | MiR 208a Regulates Mitochondrial Biogenesis in Metabolically Challenged Cardiomyocytes |
| title_sort | mir 208a regulates mitochondrial biogenesis in metabolically challenged cardiomyocytes |
| topic | cardiomyocytes metabolic syndrome miR 208a mitochondrial biogenesis bioenergetics |
| url | https://www.mdpi.com/2073-4409/10/11/3152 |
| work_keys_str_mv | AT naveenmekala mir208aregulatesmitochondrialbiogenesisinmetabolicallychallengedcardiomyocytes AT jacobkurdys mir208aregulatesmitochondrialbiogenesisinmetabolicallychallengedcardiomyocytes AT alexispaigevicenzi mir208aregulatesmitochondrialbiogenesisinmetabolicallychallengedcardiomyocytes AT leanaroseweiler mir208aregulatesmitochondrialbiogenesisinmetabolicallychallengedcardiomyocytes AT carmenavramut mir208aregulatesmitochondrialbiogenesisinmetabolicallychallengedcardiomyocytes AT edwinjvazquez mir208aregulatesmitochondrialbiogenesisinmetabolicallychallengedcardiomyocytes AT neliragina mir208aregulatesmitochondrialbiogenesisinmetabolicallychallengedcardiomyocytes AT marianagrosca mir208aregulatesmitochondrialbiogenesisinmetabolicallychallengedcardiomyocytes |