Details

Autor(en) / Beteiligte

• Eisermann, Dorothé Jenni
• Wenzel, Uwe
• Fitzenberger, Elena

Titel

Inhibition of chaperone-mediated autophagy prevents glucotoxicity in the Caenorhabditis elegans mev-1 mutant by activation of the proteasome

Ist Teil von

• Biochemical and biophysical research communications, 2017-02, Vol.484 (1), p.171-175

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Chronic hyperglycemia is a hallmark of diabetes mellitus and the main cause of diabetes-associated complications. Increased intracellular glucose levels lead to damaged proteins and in consequence disturb cellular proteostasis. As an important contributor to the maintenance and restoration of proteostasis, autophagy mediates the lysosomal degradation of damaged proteins or entire cellular organelles. In the present study we used the stress-sensitive mev-1 mutant of the nematode Caenorhabditis elegans in order to assess the role of lmp-2, a homologue of the lysosome associated membrane protein type 2A, in the context of glucotoxicity, which was achieved by feeding glucose in a liquid medium. Knockdown of lmp-2 by RNA interference completely prevented the survival reduction caused by glucose under heat stress. Those effects were associated with the prevention of (1) increased lysosome formation and (2) reduction of proteasomal activity, which were observed under glucose feeding. Finally, the survival reduction due to knockdown of ubiquitin remained unaffected by the additional lmp-2 knockdown in the absence or presence of glucose. In conclusion, our study provides evidence that lmp-2, a key player in chaperone-mediated autophagy, is functional in C. elegans, too. Inhibition of lmp-2 prevents the reduction of proteasomal activity by glucose and thereby prevents also glucotoxicity. •lmp-2, a key player in chaperone-mediated autophagy, is functional in C. elegans.•Knockdown of lmp-2 prevents glucose-induced survival reduction.•Knockdown of lmp-2 prevents increased lysosome formation due to glucose.•Knockdown of lmp-2 prevents reduction of proteasomal activity due to glucose.•Knockdown of lmp-2 did not affect survival reduction due to ubq-1 knockdown.