An Endoplasmic Reticulum ATPase Safeguards Endoplasmic Reticulum Identity by Removing Ectopically Localized Mitochondrial Proteins

Stringent targeting of membrane proteins to corresponding organelles is essential for organelle identity and functions. In addition to molecular pathways that target proteins to appropriate organelles, surveillance mechanisms clear mistargeted proteins from undesired destinations. Although Msp1 functions on the mitochondrial membrane to remove mistargeted proteins, the surveillance mechanism for the endoplasmic reticulum (ER) is not well understood. Here, we show that a conserved P5A-type ATPase CATP-8, which localizes to ER, removes ectopic mitochondrial tail-anchored (TA) and signal-anchored (SA) proteins from the ER. In catp-8 mutant, mitochondria fission protein FIS-1 mislocalizes to the ER membrane. Together with another mitochondria fission protein MFF-2, FIS-1 causes ER fragmentation in a Dynamin-related protein (DRP-1)-dependent manner. In addition, CATP-8 is essential for dendrite development. catp-8 mutant dramatically reduces the level of the dendrite guidance receptor DMA-1, leading to diminished dendritic arbors. Hence, P5A ATPase safeguards ER morphology and functions by preventing mitochondrial proteins mislocalization.