Abstract

Eukaryotic cells are equipped with an efficient quality control system to selectively eliminate misfolded and damaged proteins, and organelles. Abnormal polypeptides that escape from proteasome-dependent degradation and aggregate in the cytosol can be transported via microtubules to inclusion bodies called 'aggresomes', where misfolded proteins are confined and degraded by autophagy. Here, we show that Type 2 transglutaminase (TG2) knockout mice display impaired autophagy and accumulate ubiquitinated protein aggregates upon starvation. Furthermore, p62-dependent peroxisome degradation is also impaired in the absence of TG2. We also demonstrate that, under cellular stressful conditions, TG2 physically interacts with p62 and they are localized in cytosolic protein aggregates, which are then recruited into autophagosomes, where TG2 is degraded. Interestingly, the enzyme's crosslinking activity is activated during autophagy and its inhibition leads to the accumulation of ubiquitinated proteins. Taken together, these data indicate that the TG2 transamidating activity has an important role in the assembly of protein aggregates, as well as in the clearance of damaged organelles by macroautophagy.

Autore Pugliese

• Fimia Gian Maria

Tutti gli autori

• D'Eletto M. , Farrace M. G. , Rossin F. , Strappazzon F. , DI Giacomo G. , Cecconi F. , Melino G. , Sepe S. , Moreno S. , Fimia G .M. , Falasca L. , Nardacci R. , Piacentini M.

Titolo volume/Rivista

CELL DEATH AND DIFFERENTIATION

Anno di pubblicazione

2012

ISSN

1476-5403

ISBN

Non Disponibile

Numero di citazioni Wos

32

Ultimo Aggiornamento Citazioni

25/04/2018

Numero di citazioni Scopus

32

Ultimo Aggiornamento Citazioni

26/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile