What is it about?
This article was a research highlight (a punctum) about a JCB paper we published in 2016. In the original paper, we demonstrated that the Atg8 proteins (LC3s & GABARAPs) are not essential for trapping cargo in membrane bound compartments called autophagosomes. Instead, the Atg8 proteins were only essential to the final stages of the process known as autophagy. This punctum briefly summarizes the findings of that publication (DOI: 10.1083/jcb.201607039), which should be cited as the primary resource.
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Why is it important?
For over a decade, measurements of autophagy in mammalian cells have depended on detecting the localization, abundance and lipidation of the mammalian atg8 proteins (particularly the LC3s), because they consistently localize to autophagosomes. As a result, it has long been assumed that the Atg8 proteins are essential for making and sealing autophagosomes. Our work demonstrated that this was not the case. Atg8 proteins are entirely dispensable for building and sealing autophagosomes (even during selective autophagy). Instead, the Atg8 proteins play an essential role in the final stages of autophagy; autophagosome lysosome fusion.
Perspectives
I was originally planning on doing a postdoc abroad, but an image printed on an A4 sheet of paper changed all of that. Two weeks before submitting my doctoral thesis, Michael Lazarou approached me to see if I was interested in joining his lab. Michael needed someone with microscopy experience to analyze the knockout cell lines generated by Thanh Nguyen. That's when Michael showed me a TEM image of an autophagosome, and explained that the image was acquired in a cell lacking the genes for LC3A, LC3B, LC3C, GABARAP, GABARAP-L1 and GABARAP-L2. I didn't believe him. I spent my entire PhD studying mitophagy, yet I didn't question the importance of LC3 even once. I had so much trouble believing Michael's image. I wanted to see more proof. I accepted michael's job offer within 48 hours and gained that opportunity.
Benjamin S Padman
Monash University
Read the Original
This page is a summary of: Autophagosome formation and cargo sequestration in the absence of LC3/GABARAPs, Autophagy, February 2017, Taylor & Francis,
DOI: 10.1080/15548627.2017.1281492.
You can read the full text:
Contributors
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