title: Mitophagy and mitochondrial biogenesis in atrial tissue of patients undergoing heart surgery with cardiopulmonary bypass.
abstract: 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.
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California, USA.
authors.forename: Allen M
authors.initials: AM
authors.lastname: Andres
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California, USA.
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Tucker
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California, USA.
authors.forename: Amandine
authors.initials: A
authors.lastname: Thomas
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California, USA.
authors.forename: David Jr
authors.initials: DJ
authors.lastname: Taylor
authors.affiliation: Beaumont Hospital - Dearborn, Dearborn, Michigan, USA.
authors.forename: David
authors.initials: D
authors.lastname: Sengstock
authors.affiliation: Beaumont Hospital - Dearborn, Dearborn, Michigan, USA.
authors.forename: Salik M
authors.initials: SM
authors.lastname: Jahania
authors.affiliation: Beaumont Hospital - Dearborn, Dearborn, Michigan, USA.
authors.forename: Reza
authors.initials: R
authors.lastname: Dabir
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California, USA.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Pourpirali
authors.affiliation: Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama, Birmingham, Alabama, USA.
authors.forename: Jamelle A
authors.initials: JA
authors.lastname: Brown
authors.affiliation: Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama, Birmingham, Alabama, USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Westbrook
authors.affiliation: Department of Pathology, Division of Molecular and Cellular Pathology, University of Alabama, Birmingham, Alabama, USA.
authors.forename: Scott W
authors.initials: SW
authors.lastname: Ballinger
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Mentzer
authors.affiliation: Cedars-Sinai Heart Institute, Los Angeles, California, USA.
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Gottlieb
mesh_terms: D000368:Aged; D020517:Atrial Appendage / Q000378:metabolism*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D018797:Cell Cycle Proteins; D001026:Coronary Artery Bypass; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D063306:Mitophagy; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D001678:Organelle Biogenesis; D011132:Polyribosomes; D012333:RNA, Messenger / Q000378:metabolism*; D035582:Transcription Factor TFIIIA / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: C094297:CALCOCO2 protein, human; D018797:Cell Cycle Proteins; D004272:DNA, Mitochondrial; D026901:Membrane Transport Proteins; D009687:Nuclear Proteins; C409460:OPTN protein, human; D012333:RNA, Messenger; D035582:Transcription Factor TFIIIA; D004247:DNA; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human