Abnormal cell-clearance and accumulation of autophagic vesicles in lymphocytes from patients affected with Ataxia-Teleangiectasia

Roberta D'Assante, Anna Fusco, Loredana Palamaro, Elena V. Polishchuk, Roman S. Polishchuk, Gabriella Bianchino, Vitina Grieco, Maria Rosaria Prencipe, Andrea Ballabio, Claudio Pignata

Research output: Contribution to journalArticlepeer-review


Ataxia-Teleangiectasia (A-T) is a neurodegenerative disorder due to mutations in ATM gene. ATM in the nucleus ensures DNA repair, while its role in the cytosol is still poorly clarified. Abnormal autophagy has been documented in other neurodegenerative disorders, thus we evaluated whether alteration in this process may be involved in the pathogenesis of A-T by analyzing the autophagic vesicles and the genes implicated in the different stages of autophagy. Through transmission electron microscopy (TEM) and immunofluorescence analysis we observed an accumulation of APs associated with a LC3 puncta pattern, and a reduced number of ALs. We also documented an increased expression of genes involved in AP and lysosome biogenesis and function, and a decrease of Vps18 expression, involved in their vesicular trafficking and fusion. mTORC1-controlled proteins were hyperphosphorylated in A-T, in keeping with an increased mTOR inhibitory influence of autophagy. Betamethasone is able to promote the degradation of SQSTM1, a biomarker of autophagy. Collectively, our results indicate that in cells from A-T patients, the APs maturation is active, while the fusion between APs and lysosomes is inappropriate, thus implying abnormalities in the cell-clearance process. We also documented a positive effect of Betamethasone on molecules implicated in autophagosome degradation.

Original languageEnglish
Pages (from-to)16-25
Number of pages10
JournalClinical Immunology
Publication statusPublished - Feb 1 2017


  • Ataxia-Teleangiectasia
  • Autophagosome-lysosome fusion
  • Autophagosomes
  • Autophagy
  • Cell-clearance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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