title: Impairment of mitochondrial oxidative phosphorylation in rat fatty liver exposed to preservation-reperfusion injury.
abstract: OBJECTIVE
  As the impairment of the cellular energy metabolism contributes to the failure of fatty liver grafts after transplantation, we aimed to determine whether steatosis affects the oxidative phosphorylation activity during preservation.
  
  
  METHODS
  Rat normal and fatty livers were preserved for 18 h and then reperfused with warm oxygenated solution. The oxidative phosphorylation, the F(0)F(1)-ATPase and the Complex I activities were assessed in isolated mitochondria before and after preservation, and during reperfusion. The ALT release and portal pressure were monitored during reperfusion.
  
  
  RESULTS
  The baseline phosphorylation activity was similar in normal and steatotic mitochondria. After cold preservation, the respiratory control index and state 3 respiration decreased significantly only in steatotic livers. Reperfusion induced a further deterioration in either group. Contrary to normal liver, uncoupling of fatty liver mitochondria allowed the recovery of the maximal respiration rate only using succinate (Complex II-dependent substrate), but not glutamate-malate (Complex I-dependent). Complex I dysfunction was confirmed spectrophotometrically. The ATPase activity was also significantly lower in fatty livers. Finally, ALT release and portal pressure were greater in steatotic livers.
  
  
  CONCLUSIONS
  The alteration of the oxidative phosphorylation activity during preservation is greatly exacerbated by fatty infiltration likely resulting from damage of the respiratory chain Complex I and of the F(0)F(1)-ATP synthase.
authors.affiliation: Dipartimento di Biochimica, University of Bologna, 40138 Bologna, Italy. caraceni@med.unibo.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Caraceni
authors.forename: Cristina
authors.initials: C
authors.lastname: Bianchi
authors.forename: Marco
authors.initials: M
authors.lastname: Domenicali
authors.forename: Anna
authors.initials: A
authors.lastname: Maria Pertosa
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Maiolini
authors.forename: Giovanna
authors.initials: G
authors.lastname: Parenti Castelli
authors.forename: Bruno
authors.initials: B
authors.lastname: Nardo
authors.forename: Franco
authors.initials: F
authors.lastname: Trevisani
authors.forename: Giorgio
authors.initials: G
authors.lastname: Lenaz
authors.forename: Mauro
authors.initials: M
authors.lastname: Bernardi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D019069:Cell Respiration; D003080:Cold Temperature; D042967:Electron Transport Complex I / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism* / Q000503:physiopathology; D016031:Liver Transplantation; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000378:metabolism* / Q000503:physiopathology; D009926:Organ Preservation; D011168:Portal System; D006180:Proton-Translocating ATPases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D014475:Uncoupling Agents; D000255:Adenosine Triphosphate; D000410:Alanine Transaminase; D006180:Proton-Translocating ATPases; D042967:Electron Transport Complex I