title: Disrupted Renal Mitochondrial Homeostasis after Liver Transplantation in Rats.
abstract: BACKGROUND
  Suppressed mitochondrial biogenesis (MB) contributes to acute kidney injury (AKI) after many insults. AKI occurs frequently after liver transplantation (LT) and increases mortality. This study investigated whether disrupted mitochondrial homeostasis plays a role in AKI after LT.
  
  
  METHODS
  Livers were explanted from Lewis rats and implanted after 18 h cold storage. Kidney and blood were collected 18 h after LT.
  
  
  RESULTS
  In the kidney, oxidative phosphorylation (OXPHOS) proteins ATP synthase-β and NADH dehydrogenase-3 decreased 44% and 81%, respectively, with marked reduction in associated mRNAs. Renal PGC-1α, the major regulator of MB, decreased 57% with lower mRNA and increased acetylation, indicating inhibited synthesis and suppressed activation. Mitochondrial transcription factor-A, which controls mtDNA replication and transcription, protein and mRNA decreased 66% and 68%, respectively, which was associated with 64% decreases in mtDNA. Mitochondrial fission proteins Drp-1 and Fis-1 and mitochondrial fusion protein mitofusin-1 all decreased markedly. In contrast, PTEN-induced putative kinase 1 and microtubule-associated protein 1A/1B-light chain 3 increased markedly after LT, indicating enhanced mitophagy. Concurrently, 18- and 13-fold increases in neutrophil gelatinase-associated lipocalin and cleaved caspase-3 occurred in renal tissue. Both serum creatinine and blood urea nitrogen increased >2 fold. Mild to moderate histological changes were observed in the kidney, including loss of brush border, vacuolization of tubular cells in the cortex, cast formation and necrosis in some proximal tubular cells. Finally, myeloperoxidase and ED-1 also increased, indicating inflammation.
  
  
  CONCLUSIONS
  Suppression of MB, inhibition of mitochondrial fission/fusion and enhancement of mitophagy occur in the kidneys of recipients of liver grafts after long cold storage, which may contribute to the occurrence of AKI and increased mortality after LT.
authors.affiliation: Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America; The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
authors.forename: Qinlong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Yasodha
authors.initials: Y
authors.lastname: Krishnasamy
authors.affiliation: Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Hasibur
authors.initials: H
authors.lastname: Rehman
authors.affiliation: Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America; Department of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, United States of America.
authors.forename: John J
authors.initials: JJ
authors.lastname: Lemasters
authors.affiliation: Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina, United States of America.
authors.forename: Rick G
authors.initials: RG
authors.lastname: Schnellmann
authors.affiliation: Department of Drug Discovery & Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina, United States of America.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhong
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D006706:Homeostasis; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D063306:Mitophagy; D001678:Organelle Biogenesis; D010085:Oxidative Phosphorylation; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D014157:Transcription Factors