Maintaining Golgi Homeostasis: A Balancing Act of Two Proteolytic Pathways

Abstract

The Golgi apparatus is a central hub for cellular protein trafficking and signaling. Golgi structure and function is tightly coupled and undergoes dynamic changes in health and disease. A crucial requirement for maintaining Golgi homeostasis is the ability of the Golgi to target aberrant, misfolded, or otherwise unwanted proteins to degradation. Recent studies have revealed that the Golgi apparatus may degrade such proteins through autophagy, retrograde trafficking to the ER for ER-associated degradation (ERAD), and locally, through Golgi apparatus-related degradation (GARD). Here, we review recent discoveries in these mechanisms, highlighting the role of the Golgi in maintaining cellular homeostasis.

Keywords: EGAD; GARD; GOMED; Golgi; autophagy; proteasomal degradation; proteostasis.

Figure 1

Proteasomal degradation and the Golgi. (A). Under conditions of Golgi stress, the structural Golgin protein GM130 is ubiquitinated and targeted for degradation by proteasomes, bound to the cytosolic side of the Golgi membrane. This process, known as Golgi apparatus-related degradation (GARD) allows the Golgi to regulate its morphology quickly in response to stress [32]. (B). In yeast, endosome and Golgi-associated degradation (EGAD) has been described as a mechanism by which proteins can be ubiquitinated by the Dsc complex, released from the Golgi membrane by VCP/CDC48 and degraded by cytosolic proteasomes [31].

Figure 2

The Golgi apparatus in autophagy. (A). Atg9 actively cycles between the Golgi apparatus and endosomes [43,44]. Upon initiation of autophagy, Golgi-to-endosome trafficking is inhibited, causing Atg9 to preferentially localize to the Golgi [45]. (B). Atg9 is then trafficked to nascent phagophore structures to support initiation of autophagy, in vesicles that contain PI4KIIα and PI4KIIβ [46,47,48,49,50]. This step provides both membranes and phosphoinositide lipid modifying enzymes crucial for initiation of autophagy. (C). At steady state, the autophagy-associated protein GABARAP, binds GM130 at the Golgi apparatus. Under starvation conditions, competitive binding of WAC to GM130 releases GABARAP to perform its role in initiation of autophagy [51,52,53].