Many faces of mitochondrial uncoupling during age: Damage or defense?

Francesco Bellanti, Antonino Davide Romano, Anna Maria Giudetti, Tiziana Rollo, Maria Blonda, Rosanna Tamborra, Gianluigi Vendemiale, Gaetano Serviddio

Research output: Contribution to journalArticlepeer-review


An increased mitochondrial proton leak occurs in aging, but the origin of such modification remains unclear. This study defined the cause of mitochondrial uncoupling in mitotic (liver) and postmitotic (heart) rat tissues during aging and its effects on energy homeostasis and free radical production. Proton leak in old heart mitochondria was dependent on uncoupling proteins' upregulation, whereas it was caused by alterations in the mitochondrial membrane composition in old liver. ATP homeostasis was impaired in both tissues from old animals and was associated to disrupted F0F1-ATPase activity. H 2O2 production rate and 4-hydroxy-2-nonenalprotein adducts were higher in old liver mitochondria compared with young liver mitochondria, but they were similar in heart mitochondria from both groups. Moreover, key mitochondrial biogenesis regulators were upregulated in old liver but downregulated in old heart. In conclusion, uncoupling proteins mediate proton leak and avoid oxidative damage in heart, acting as a protective mechanism. This does not occur in liver, where ATP depletion and oxidative stress may stimulate mitochondrial biogenesis and eliminate damaged cells.

Original languageEnglish
Pages (from-to)892-902
Number of pages11
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number8
Publication statusPublished - Aug 2013


  • Mitochondrial biogenesis
  • Mitochondrial proton leak
  • Oxidative stress
  • Uncoupling proteins

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology
  • Medicine(all)


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