Mitophagy and mitochondrial biogenesis in atrial tissue of patients undergoing heart surgery with cardiopulmonary bypass
| Autor: | David Sengstock, David J. R. Taylor, Salik Jahania, Amandine Thomas, Somayeh Pourpirali, Jamelle A. Brown, Reza Dabir, Scott W. Ballinger, David G. Westbrook, Kyle C Tucker, Robert M. Mentzer, Allen M. Andres, Roberta A. Gottlieb |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Mitochondrial DNA medicine.medical_specialty DNA damage Mitochondrial Turnover Ubiquitin-Protein Ligases Ischemia Cell Cycle Proteins Myocardial Reperfusion Injury 030204 cardiovascular system & hematology DNA Mitochondrial Parkin GTP Phosphohydrolases 03 medical and health sciences 0302 clinical medicine Transcription Factor TFIIIA Mitophagy Humans Medicine Atrial Appendage RNA Messenger Cardiac Surgical Procedures Coronary Artery Bypass Aged Heart Valve Prosthesis Implantation Cardiopulmonary Bypass Organelle Biogenesis business.industry Membrane Transport Proteins Nuclear Proteins DNA General Medicine Middle Aged medicine.disease Surgery 030104 developmental biology Mitochondrial biogenesis Polyribosomes Female Organelle biogenesis business Research Article DNA Damage |
| Zdroj: | JCI Insight. 2 |
| ISSN: | 2379-3708 |
| Popis: | Mitophagy occurs during ischemia/reperfusion (I/R) and limits oxidative stress and injury. Mitochondrial turnover was assessed in patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB). Paired biopsies of right atrial appendage before initiation and after weaning from CPB were processed for protein analysis, mitochondrial DNA/nuclear DNA ratio (mtDNA:nucDNA ratio), mtDNA damage, mRNA, and polysome profiling. Mitophagy in the post-CPB samples was evidenced by decreased levels of mitophagy adapters NDP52 and optineurin in whole tissue lysate, decreased Opa1 long form, and translocation of Parkin to the mitochondrial fraction. PCR analysis of mtDNA comparing amplification of short vs. long segments of mtDNA revealed increased damage following cardiac surgery. Surprisingly, a marked increase in several mitochondria-specific protein markers and mtDNA:nucDNA ratio was observed, consistent with increased mitochondrial biogenesis. mRNA analysis suggested that mitochondrial biogenesis was traniscription independent and likely driven by increased translation of existing mRNAs. These findings demonstrate in humans that both mitophagy and mitochondrial biogenesis occur during cardiac surgery involving CPB. We suggest that mitophagy is balanced by mitochondrial biogenesis during I/R stress experienced during surgery. Mitigating mtDNA damage and elucidating mechanisms regulating mitochondrial turnover will lead to interventions to improve outcome after I/R in the setting of heart disease. |
| Databáze: | OpenAIRE |
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