Proteomic analysis identifies prohibitin down-regulation as a crucial event in the mitochondrial damage observed in HIV-infected patients

Vittoria Pagliarini, Fabiola Ciccosanti, Marco Corazzari, Fabio Soldani, Paola Matarrese, Valentina Iadevaia, Antonella Tinari, Mauro Zaccarelli, Jean-Luc Perfettini, Walter Malorni, Guido Kroemer, Gian Maria Fimia, Mauro Piacentini

Risultato della ricerca: Contributo in rivistaArticolo in rivista

15 Citazioni (Scopus)

Abstract

Background: Highly active antiretroviral therapy (HAART) has largely reduced the occurrence of AIDS-related diseases and death in HIV-infected patients. However, HAART produces serious side effects mainly attributed to mitochondrial toxicity. Methods: To elucidate the molecular basis of HAART-related dysfunctions, we analysed the mitochondrial proteome of peripheral blood mononuclear cells from HIV-infected patients using two-dimensional gel electrophoresis and MALDI-TOF/TOF mass spectrometry. Proteomic analysis was performed on HIV patients who were either treatment- naive or under HAART therapy including zidovudine or stavudine as nucleoside reverse transcriptase inhibitors (NRTIs). Results: As compared to healthy donors, HAART-treated HIV-infected patients exhibited decreased levels of mitochondrial enzymes associated with energy production as well as mitochondrial chaperones. Moreover, significant alterations in the mitochondria-cytoskeleton network were observed. Notably, most of these changes were already detectable in untreated HIV carriers and persisted or worsened after HAART, indicating that relevant mitochondrial alterations were initially caused by HIV infection. Finally, in vitro experiments aimed at validating the proteomic results showed that down-regulation of the mitochondrial chaperone prohibitin is a causative event in NRTI-induced mitochondrial damage. Conclusions: Our results indicate a major role of HIV infection in the mitochondrial toxicity of HAART-treated patients and identify novel candidate markers for assessing the risk of HIV- and HAART-related pathologies. ©2010 International Medical Press.
Lingua originaleEnglish
pagine (da-a)377-390
Numero di pagine14
RivistaAntiviral Therapy
Volume15
DOI
Stato di pubblicazionePubblicato - 2010

Keywords

  • Anti-HIV Agents
  • Antiretroviral Therapy, Highly Active
  • Down-Regulation
  • Electrophoresis, Gel, Two-Dimensional
  • HIV Infections
  • HIV-1
  • Humans
  • Mitochondria
  • Proteomics
  • Repressor Proteins
  • Reverse Transcriptase Inhibitors
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Stavudine
  • Zidovudine

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