An endoplasmic reticulum (ER) ATPase safeguards ER identity by removing ectopically localized mitochondrial proteins

Abstract

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. While Msp1 functions on mitochondrial membrane to remove mistargeted proteins, the surveillance mechanism for the ER is not well understood. Here, we show that mitochondrial tail-anchored (TA) and signal-anchored (SA) proteins mislocalize to ER membrane in neurons and muscles in C. elegans catp-8 mutants. catp-8 encodes a conserved P5A type ATPase, which localizes to ER and removes ectopic mitochondrial TA/SA proteins from ER. In catp-8 mutant, mitochondria fission protein FIS-1 mislocalizes to ER membrane. Together with another mitochondria fission protein MFF-2, FIS-1 causes ER fragmentation in a Dynamin related protein (DRP-1) dependent manner. Additionally, 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. HIGHLIGHTSCATP-8, a P5A type ATPase, localizes to ER and functions as a surveillance mechanism to remove mistargeted mitochondrial proteins. Multiple mitochondria proteins are mistargeted to ER in catp-8 mutants. Ectopic recruitment of mitochondria fission mechinary to ER causes ER fragmentation in catp-8 mutants. CATP-8 is essential for PVD dendrite morphogenesis through modulating the level of transmembrane receptor DMA-1.