"Discovery of Atg5/Atg7-independent alternative macroautophagy"

Macroautophagy is a process that leads to the bulk degradation of sub-cellular constituents by producing autophagosomes/autolysosomes. It is believed that Atg5 and Atg7 are essential genes for macroautophagy. However, we show that cells lacking Atg5 or Atg7 can still form autophagosomes/autolysosomes and perform autophagy-mediated protein degradation when subjected to certain stressors. Although lipidation of LC3 (LC3-II formation) is generally considered to be a good indicator of macroautophagy, it did not occur during the Atg5/Atg7-independent alternative process of macroautophagy. We also found that this alternative process of macroautophagy was regulated by several autophagic proteins, including Ulk1 and Beclin 1. Unlike conventional macroautophagy, autophagosomes seemed to be generated in a Rab9-dependent manner by the fusion of isolation membranes with vesicles derived from the trans-Golgi and late endosomes. In vivo, Atg5-independent alternative macroautophagy was detected in several embryonic tissues. It also played a role in clearing mitochondria during erythroid maturation. These results indicate that mammalian macroautophagy can occur via at least two different pathways, which are an Atg5/Atg7-dependent conventional pathway and an Atg5/Atg7-independent alternative pathway.