Abstract
The endoplasmic reticulum (ER) is a dynamic membrane system comprising different and interconnected subdomains. The ER structure changes in response to different stress conditions through the activation of a selective autophagic pathway called ER-phagy. This represents a quality control mechanism for ER turnover and component recycling. Several ER-resident proteins have been indicated as receptors for ER-phagy; among these, there are proteins characterized by the presence of a reticulon homology domain (RHD). RHD-containing proteins promote ER fragmentation by a mechanism that involves LC3 binding and lysosome delivery. Moreover, the presence of a correct RHD structure is closely related to their capability to regulate ER shape and morphology by curvature induction and membrane remodeling. Deregulation of the ER-selective autophagic pathway due to defects in proteins with RHD has been implicated in several human diseases, infectious and neurodegenerative diseases in particular, as well as in cancer development. While the molecular mechanisms and the physiological role of ER-phagy are not yet fully understood, it is quite clear that this process is involved in different cellular signaling pathways and has an impact in several human pathologies.
Highlights
The endoplasmic reticulum (ER) is a wide and interconnected system of cell membranes forming a network with a common luminal space
It is classified into smooth ER (SER) and rough ER (RER); the first is devoid of ribosomes and is characterized by a tubular structure, while the RER shows a sheet-like morphology and the presence of ribosomes (Chen et al, 2013)
Recent studies have demonstrated that, under stress conditions caused by different stimuli (Moretti et al, 2017; Fregno and Molinari, 2018; Smith et al, 2018), ER fragments are eliminated by a distinct form of autophagy called ER-phagy, which regulates ER remodeling and represents an ER quality control mechanism (Grumati et al, 2018)
Summary
The endoplasmic reticulum (ER) is a wide and interconnected system of cell membranes forming a network with a common luminal space. ER is a complex organelle composed of different dynamic subdomains, sheets, tubules, and a nuclear envelope, continuously remodeled to maintain cellular homeostasis (Schwarz and Blower, 2016). It is classified into smooth ER (SER) and rough ER (RER); the first is devoid of ribosomes and is characterized by a tubular structure, while the RER shows a sheet-like morphology and the presence of ribosomes (Chen et al, 2013). The dynamic changes of the ER depend on the activation of different pathways: ER-stress activated autophagy, which can induce ER expansion through the generation of membrane sheets (Schuck et al, 2009), or selective ER-phagy, which regulates ER turnover by a more specific mechanism (Grumati et al, 2018)
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