Atlastins mediate selective autophagy of the endoplasmic reticulum

Importance

Autophagy is a process of ‘self-eating’ employed by cells to balance energy and nutrient supplies, as well as clean up and recycle protein aggregates and damaged organelles. Due to its importance in neurodegenerative diseases, autophagy of mitochondria (mitophagy) has been the focus of extensive research over the past couple of decades and our understanding of its mechanism is growing fast. In contrast, study of the mechanisms that underlie the degradation of other organelles, such as the endoplasmic reticulum (ER), has fallen behind. In part this may be due to technical challenges. The ER is the largest organelle in eukaryotic cells, comprising a predicted 10% of the cell volume and half the cell membranes. Detecting the removal of small amounts of such a huge structure during ER-phagy thus poses a significant challenge to researchers. This study by Liang et al not only identifies the membrane remodelling proteins Atlastins as part of the ER-phagy machinery, but also presents two new, simple assays for monitoring this process. This has great potential for encouraging further research in this area.

Key findings

In this study the authors develop two assays with sufficient sensitivity to observe serum starvation-induced ER-phagy – EATR, a reporter-based assay suitable for both imaging and FACs, and CCER, a western blot-based assay. They then use these assays to monitor ER-phagy in Atlastin knockout cell lines and show that:

• Atlastin family members are required for efficient ER-phagy.
• ATL2 acts downstream of FAM134B (which recruits autophagy proteins to membranes)
• The membrane remodelling function of Atlastin is required for ER-phagy.

They thus conclude Atlastin proteins have a role in isolating regions of the ER undergoing autophagy from the rest of the organelle.

Why I chose this paper

I chose this paper as it sheds light on a key step of the ER-phagy process that was previously a mystery – the separation of ER autophagic membranes from the rest of the organelle. I also think the methods developed here seem simple to use and effective and so will be of interest to anyone studying autophagy.

(1 votes)