Autophagy is a cellular degradation process that entails sequestration of cytoplasmic material by double-membrane autophagosomes. When an autophagosome fuses with a lysosome, the degradative enzymes of the lysosome will degrade the sequestered material. The autophagosome is formed from a structure called the phagophore, but it has remained unclear where the phagophore comes from and how it is shaped into an autophagosome.
Subdomains of the endoplasmic reticulum (ER) known as omegasomes (because of their omega shape in fluorescence microscopy), which are characterized by the protein DFCP1, have been proposed to promote shaping of phagophores,
Now, researcher Viola Nähse and her co-workers in Harald Stenmark´s group, in collaboration with associate professor Kay Schink, have shown that DFCP1 is an ATPase that constricts omegasomes and in this way promotes autophagosome formation. Its activity is particularly important for the formation of large autophagosomes involved in selective autophagy of large cytoplasmic objects such as damaged mitochondria and protein aggregates.
Selective autophagy plays crucial roles in preventing both cancer development and neurodegenerative diseases, and the current findings are therefore particularly interesting in this context.
The Nature Communications article:
ATPase activity of DFCP1 controls selective autophagy.
Nähse V, Raiborg C, Tan KW, Mørk S, Torgersen ML, Wenzel EM, Nager M, Salo VT, Johansen T, Ikonen E, Schink KO, Stenmark H.
Nat Commun. 2023 Jul 8;14(1):4051. doi: 10.1038/s41467-023-39641-9.
Viola Nähse, first author