Cargando…

Implications of Activating the ANT2/mTOR/PGC-1α Feedback Loop: Insights into Mitochondria-Mediated Injury in Hypoxic Myocardial Cells

Mitochondrial dysfunction is known to play a critical role in the development of cardiomyocyte death during acute myocardial infarction (AMI). However, the exact mechanisms underlying this dysfunction are still under investigation. Adenine nucleotide translocase 2 (ANT2) is a key functional protein...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Meng, Yang, Yuanzhan, Zhu, Zhu, Chen, Zixuan, Huang, Dongyang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670450/
https://www.ncbi.nlm.nih.gov/pubmed/37998720
http://dx.doi.org/10.3390/cimb45110543
_version_ 1785139925963767808
author Zhang, Meng
Yang, Yuanzhan
Zhu, Zhu
Chen, Zixuan
Huang, Dongyang
author_facet Zhang, Meng
Yang, Yuanzhan
Zhu, Zhu
Chen, Zixuan
Huang, Dongyang
author_sort Zhang, Meng
collection PubMed
description Mitochondrial dysfunction is known to play a critical role in the development of cardiomyocyte death during acute myocardial infarction (AMI). However, the exact mechanisms underlying this dysfunction are still under investigation. Adenine nucleotide translocase 2 (ANT2) is a key functional protein in mitochondria. We aimed at exploring the potential benefits of ANT2 inhibition against AMI. We utilized an oxygen–glucose deprivation (OGD) cell model and an AMI mice model to detect cardiomyocyte injury. We observed elevated levels of reactive oxygen species (ROS), disrupted mitochondrial membrane potential (MMP), and increased apoptosis due to the overexpression of ANT2. Additionally, we discovered that ANT2 is involved in myocardial apoptosis by activating the mTOR (mechanistic target of rapamycin kinase)-dependent PGC-1α (PPARG coactivator 1 alpha) pathway, establishing a novel feedback loop during AMI. In our experiments with AC16 cells under OGD conditions, we observed protective effects when transfected with ANT2 siRNA and miR-1203. Importantly, the overexpression of ANT2 counteracted the protective effect resulting from miR-1203 upregulation in OGD-induced AC16 cells. All these results supported that the inhibition of ANT2 could alleviate myocardial cell injury under OGD conditions. Based on these findings, we propose that RNA interference (RNAi) technology, specifically miRNA and siRNA, holds therapeutic potential by activating the ANT2/mTOR/PGC-1α feedback loop. This activation could help mitigate mitochondria-mediated injury in the context of AMI. These insights may contribute to the development of future clinical strategies for AMI.
format Online
Article
Text
id pubmed-10670450
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-106704502023-10-27 Implications of Activating the ANT2/mTOR/PGC-1α Feedback Loop: Insights into Mitochondria-Mediated Injury in Hypoxic Myocardial Cells Zhang, Meng Yang, Yuanzhan Zhu, Zhu Chen, Zixuan Huang, Dongyang Curr Issues Mol Biol Article Mitochondrial dysfunction is known to play a critical role in the development of cardiomyocyte death during acute myocardial infarction (AMI). However, the exact mechanisms underlying this dysfunction are still under investigation. Adenine nucleotide translocase 2 (ANT2) is a key functional protein in mitochondria. We aimed at exploring the potential benefits of ANT2 inhibition against AMI. We utilized an oxygen–glucose deprivation (OGD) cell model and an AMI mice model to detect cardiomyocyte injury. We observed elevated levels of reactive oxygen species (ROS), disrupted mitochondrial membrane potential (MMP), and increased apoptosis due to the overexpression of ANT2. Additionally, we discovered that ANT2 is involved in myocardial apoptosis by activating the mTOR (mechanistic target of rapamycin kinase)-dependent PGC-1α (PPARG coactivator 1 alpha) pathway, establishing a novel feedback loop during AMI. In our experiments with AC16 cells under OGD conditions, we observed protective effects when transfected with ANT2 siRNA and miR-1203. Importantly, the overexpression of ANT2 counteracted the protective effect resulting from miR-1203 upregulation in OGD-induced AC16 cells. All these results supported that the inhibition of ANT2 could alleviate myocardial cell injury under OGD conditions. Based on these findings, we propose that RNA interference (RNAi) technology, specifically miRNA and siRNA, holds therapeutic potential by activating the ANT2/mTOR/PGC-1α feedback loop. This activation could help mitigate mitochondria-mediated injury in the context of AMI. These insights may contribute to the development of future clinical strategies for AMI. MDPI 2023-10-27 /pmc/articles/PMC10670450/ /pubmed/37998720 http://dx.doi.org/10.3390/cimb45110543 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Meng
Yang, Yuanzhan
Zhu, Zhu
Chen, Zixuan
Huang, Dongyang
Implications of Activating the ANT2/mTOR/PGC-1α Feedback Loop: Insights into Mitochondria-Mediated Injury in Hypoxic Myocardial Cells
title Implications of Activating the ANT2/mTOR/PGC-1α Feedback Loop: Insights into Mitochondria-Mediated Injury in Hypoxic Myocardial Cells
title_full Implications of Activating the ANT2/mTOR/PGC-1α Feedback Loop: Insights into Mitochondria-Mediated Injury in Hypoxic Myocardial Cells
title_fullStr Implications of Activating the ANT2/mTOR/PGC-1α Feedback Loop: Insights into Mitochondria-Mediated Injury in Hypoxic Myocardial Cells
title_full_unstemmed Implications of Activating the ANT2/mTOR/PGC-1α Feedback Loop: Insights into Mitochondria-Mediated Injury in Hypoxic Myocardial Cells
title_short Implications of Activating the ANT2/mTOR/PGC-1α Feedback Loop: Insights into Mitochondria-Mediated Injury in Hypoxic Myocardial Cells
title_sort implications of activating the ant2/mtor/pgc-1α feedback loop: insights into mitochondria-mediated injury in hypoxic myocardial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670450/
https://www.ncbi.nlm.nih.gov/pubmed/37998720
http://dx.doi.org/10.3390/cimb45110543
work_keys_str_mv AT zhangmeng implicationsofactivatingtheant2mtorpgc1afeedbackloopinsightsintomitochondriamediatedinjuryinhypoxicmyocardialcells
AT yangyuanzhan implicationsofactivatingtheant2mtorpgc1afeedbackloopinsightsintomitochondriamediatedinjuryinhypoxicmyocardialcells
AT zhuzhu implicationsofactivatingtheant2mtorpgc1afeedbackloopinsightsintomitochondriamediatedinjuryinhypoxicmyocardialcells
AT chenzixuan implicationsofactivatingtheant2mtorpgc1afeedbackloopinsightsintomitochondriamediatedinjuryinhypoxicmyocardialcells
AT huangdongyang implicationsofactivatingtheant2mtorpgc1afeedbackloopinsightsintomitochondriamediatedinjuryinhypoxicmyocardialcells