BBB webinar: Terje Johansen

Terje Johansen
Department of Medical Biology, University of Tromsø – The Arctic University of Norway, Tromsø

Selective autophagy, the selective degradation of macromolecules or organelles by autophagy, is a crucial quality control process vital for cellular homeostasis and prevention of disease. Cargoes to be degraded are recognized by selective autophagy receptors, like the sequestosome 1/p62-like receptors (SLRs). p62/SQSTM1 and other SLRs couple cargo to the forming autophagosomes, called phagophores, via interactions with the ATG8 family of proteins through a short motif in the autophagy receptors, the LIR motif.

The endoplasmic reticulum (ER) is the largest membrane-bound organelle in eukaryotic cells and plays critical roles in diverse processes in metabolism, signaling and intracellular organization. In response to stress stimuli such as nutrient deprivation, accumulation of misfolded proteins or exposure to chemicals, the ER increases in size through upregulated synthesis of its components to counteract the stress. To restore physiological size, the excess ER components are continuously dismantled and degraded by ER-phagy, a form of autophagy that targets, via selective autophagy receptors, specific ER portions to the lysosome for degradation. Previous studies have revealed six ER resident proteins as ER-phagy receptors. We have now identified CALCOCO1 as a soluble ER-phagy receptor for the degradation of tubular ER in response to proteotoxic and starvation-induced stress. We also found that CALCOCO1 acts as a receptor for autophagic degradation of Golgi (Golgiphagy) during nutrient starvation. Depletion of CALCOCO1 causes expansion of the Golgi and accumulation of its structural and membrane proteins.

Chairperson: Jaakko Saraste, Department of Biomedicine