Prohibitin-1 deficiency promotes inflammation and increases sensitivity to liver injury

Virginia Sánchez-Quiles, Víctor Segura, Emilie Bigaud, Bin He, Bert W. O'Malley, Enrique Santamaría, Jesús Prieto, Fernando J. Corrales

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Liver diseases are the fifth cause of mortality in Western countries, and as opposed to other major causes of mortality, their incidence is increasing. Understanding the molecular background contributing to the progression of liver ailments will surely open new perspectives for the better management of patients. The aim of this study is to elucidate mechanisms underlying the progression of liver injury associated with deficient prohibitin 1, an essential protein to maintain mitochondrial homeostasis and gene expression. PHB1+/- mice developed a more severe steatohepatitis than WT littermates when exposed to a choline and methionine deficient diet. The increased sensitivity was mediated by mitochondrial dysfunction and metabolic impairment in PHB1+/- livers, including inactivation of AMP kinase, measured under a non-restricted diet. Moreover, pro-inflammatory challenges induced higher mortality and liver injury in PHB. +/- mice. The increased proliferative capacity of PHB+/- splenocytes, resulting from constitutive defects in central molecular pathways as stated by deregulation of GSK3β, Erk, Akt or SHP-1, and the concomitant overproduction of pro-inflammatory mediators in Phb1 deficient mice, might account for these effects. In light of these results it might be concluded that Phb1 deficiency is a potential driver of chronic liver diseases by inducing hepatocyte damage and inflammation.

Original languageEnglish (US)
Pages (from-to)5783-5792
Number of pages10
JournalJournal of Proteomics
Volume75
Issue number18
DOIs
StatePublished - Oct 22 2012

Keywords

  • Inflammation
  • Liver injury
  • Prohibitin 1
  • Proteomics

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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