RGD Reference Report - Disrupted Renal Mitochondrial Homeostasis after Liver Transplantation in Rats. - Rat Genome Database

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Disrupted Renal Mitochondrial Homeostasis after Liver Transplantation in Rats.

Authors: Liu, Qinlong  Krishnasamy, Yasodha  Rehman, Hasibur  Lemasters, John J  Schnellmann, Rick G  Zhong, Zhi 
Citation: Liu Q, etal., PLoS One. 2015 Oct 19;10(10):e0140906. doi: 10.1371/journal.pone.0140906. eCollection 2015.
RGD ID: 12910862
Pubmed: PMID:26480480   (View Abstract at PubMed)
PMCID: PMC4610703   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0140906   (Journal Full-text)


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-ß 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.
CONCLUSION: 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FIS1Humanacute kidney failure  ISOFis1 (Rattus norvegicus)protein:decreased expression:kidney (rat)RGD 
Fis1Ratacute kidney failure  IEP protein:decreased expression:kidney (rat)RGD 
Fis1Mouseacute kidney failure  ISOFis1 (Rattus norvegicus)protein:decreased expression:kidney (rat)RGD 
MFN1Humanacute kidney failure  ISOMfn1 (Rattus norvegicus)protein:decreased expression:kidney (rat)RGD 
Mfn1Ratacute kidney failure  IEP protein:decreased expression:kidney (rat)RGD 
Mfn1Mouseacute kidney failure  ISOMfn1 (Rattus norvegicus)protein:decreased expression:kidney (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Fis1  (fission, mitochondrial 1)
Mfn1  (mitofusin 1)

Genes (Mus musculus)
Fis1  (fission, mitochondrial 1)
Mfn1  (mitofusin 1)

Genes (Homo sapiens)
FIS1  (fission, mitochondrial 1)
MFN1  (mitofusin 1)


Additional Information