Lifelong maintenance of composition, function and cellular/subcellular distribution of proteasomes in human liver

Elena Bellavista, Morena Martucci, Francesco Vasuri, Aurelia Santoro, Michele Mishto, Alexander Kloss, Elisa Capizzi, Alessio Degiovanni, Catia Lanzarini, Daniel Remondini, Alessandro Dazzi, Sara Pellegrini, Matteo Cescon, Miriam Capri, Stefano Salvioli, Antonia D'Errico-Grigioni, Burkhardt Dahlmann, Gian Luca Grazi, Claudio Franceschi

Research output: Contribution to journalArticle

Abstract

Owing to organ shortage, livers from old donors are increasingly used for transplantation. The function and duration of such transplanted livers are apparently comparable to those from young donors, suggesting that, despite some morphological and structural age-related changes, no major functional changes do occur in liver with age. We tested this hypothesis by performing a comprehensive study on proteasomes, major cell organelles responsible for proteostasis, in liver biopsies from heart-beating donors. Oxidized and poly-ubiquitin conjugated proteins did not accumulate with age and the three major proteasome proteolytic activities were similar in livers from young and old donors. Analysis of proteasomes composition showed an age-related increased of β5i/α4 ratio, suggesting a shift toward proteasomes containing inducible subunits and a decreased content of PA28α subunit, mainly in the cytosol of hepatocytes. Thus our data suggest that, proteasomes activity is well preserved in livers from aged donors, concomitantly with subtle changes in proteasome subunit composition which might reflect the occurrence of a functional remodelling to maintain an efficient proteostasis. Gender differences are emerging and they deserve further investigations owing to the different aging trajectories between men and women. Finally, our data support the safe use of livers from old donors for transplantation.

Original languageEnglish
Pages (from-to)26-34
Number of pages9
JournalMechanisms of Ageing and Development
Volume141-142
DOIs
Publication statusPublished - Nov 1 2014

Keywords

  • Aging
  • Gender
  • Human liver
  • Immunoproteasome
  • PA28αβ regulator
  • Standard proteasome

ASJC Scopus subject areas

  • Ageing
  • Developmental Biology
  • Medicine(all)

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  • Cite this

    Bellavista, E., Martucci, M., Vasuri, F., Santoro, A., Mishto, M., Kloss, A., Capizzi, E., Degiovanni, A., Lanzarini, C., Remondini, D., Dazzi, A., Pellegrini, S., Cescon, M., Capri, M., Salvioli, S., D'Errico-Grigioni, A., Dahlmann, B., Grazi, G. L., & Franceschi, C. (2014). Lifelong maintenance of composition, function and cellular/subcellular distribution of proteasomes in human liver. Mechanisms of Ageing and Development, 141-142, 26-34. https://doi.org/10.1016/j.mad.2014.09.003