Abstract
Autophagic degradation of parts of the nucleus (nucleophagy) and endoplasmic reticulum (ER-phagy) utilizes the selective autophagy receptors, Atg39 and Atg40, that link their target structures to the autophagy machinery. Here, we show that a complex of three proteins, Apq12, Brr6, and Brl1, is needed for both Atg39-dependent nucleophagy and Atg40-dependent ER-phagy. Apq12, Brr6, and Brl1 each have two transmembrane domains flanking a luminal region that contains an amphipathic helix. The Apq12/Brr6/Brl1 complex has been implicated in membrane remodeling during nuclear pore formation. While autophagosomal flux is unaffected by the loss of Apq12, Brr6, or Brl1, vacuolar delivery of outer and inner nuclear membrane proteins (Hmg1, Nvj1, and Src1), pan-ER proteins (Sec63 and Per33), and an ER tubule junction protein (Lnp1) is blocked. In
apq12Δ
cells, Atg39 and Atg40 receptors concentrate in puncta and associate with the autophagic machinery; however, their delivery to the vacuole is blocked. Atg39 puncta extend into the cytoplasm but fail to detach from the nuclear envelope (NE), suggesting a defect in membrane scission. Coimmunoprecipitation and crosslinking analysis indicate that Atg39 and Atg40 interact with the Apq12/Brr6/Brl1 complex. We propose that the membrane remodeling activity of the Apq12/Brr6/Brl1 complex is needed to release fragments of the NE and ER so they can be sequestered within autophagosomes for degradation.