Eukaryotic cells are equipped with a very efficient quality control system to selectively eliminate misfolded and damaged proteins and organelles. Autophagy is the major intracellular degradation/recycling catabolic system for mutated/ misfolded proteins and damaged organelles. It is a highly complex regulated process that plays a key role in cellular maintenance and development. Autophagy is recognized to play an important role in the pathogenesis of the major human diseases. Interestingly, recent studies have demonstrated that autophagy is not a simple metabolite recycling system, but also has the ability to degrade specific cellular targets, such as mitochondria, peroxisomes, cilia, and bacteria. In this chapter the involvement of TG2 in the autophagic pathway is discussed. Indeed, cells or mouse lacking the enzyme show impaired autophagy and accumulate ubiquitinated protein aggregates and damaged mitochondria. TG2 physically interacts with the autophagy cargo protein 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 indicating that TG2 plays an important role in the assembly of protein aggregates as well as for the clearance of damaged organelles. Interestingly cells lacking the enzyme display impaired autophagy/mitophagy and as a consequence shift their metabolism to glycolysis.
D'Eletto, M., Rossin, F., Farrace, M.g., Piacentini, M. (2016). The role of transglutaminase type 2 in the regulation of autophagy. In Transglutaminases: Multiple Functional Modifiers and Targets for New Drug Discovery (pp. 171-191). Springer Japan [10.1007/978-4-431-55825-5_8].
The role of transglutaminase type 2 in the regulation of autophagy
D'Eletto M.;Rossin F.;Farrace M. G.;Piacentini M.
2016-01-01
Abstract
Eukaryotic cells are equipped with a very efficient quality control system to selectively eliminate misfolded and damaged proteins and organelles. Autophagy is the major intracellular degradation/recycling catabolic system for mutated/ misfolded proteins and damaged organelles. It is a highly complex regulated process that plays a key role in cellular maintenance and development. Autophagy is recognized to play an important role in the pathogenesis of the major human diseases. Interestingly, recent studies have demonstrated that autophagy is not a simple metabolite recycling system, but also has the ability to degrade specific cellular targets, such as mitochondria, peroxisomes, cilia, and bacteria. In this chapter the involvement of TG2 in the autophagic pathway is discussed. Indeed, cells or mouse lacking the enzyme show impaired autophagy and accumulate ubiquitinated protein aggregates and damaged mitochondria. TG2 physically interacts with the autophagy cargo protein 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 indicating that TG2 plays an important role in the assembly of protein aggregates as well as for the clearance of damaged organelles. Interestingly cells lacking the enzyme display impaired autophagy/mitophagy and as a consequence shift their metabolism to glycolysis.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
