The correct positioning of membrane proteins on the corresponding organelles is important for maintaining the specific “identity” and physiological functions of the organelles. The correct positioning of membrane proteins relies on precise protein sorting pathways and requires corresponding mechanisms on organelles to eliminate mislocated proteins. For example, the AAA-ATPase Msp1 of the outer mitochondrial membrane can remove the protein that is incorrectly located on the outer mitochondrial membrane. However, what mechanism on the endoplasmic reticulum (ER) helps to remove the wrongly located membrane proteins remains to be explored.

 

Dr. Xiangming Wang from the Institute of Biophysics of the Chinese Academy of Sciences and Kang Shen, a professor at Stanford University, jointly published a research paper entitled “An Endoplasmic Reticulum ATPase Safeguards Endoplasmic Reticulum Identity by Removing Ectopically Localized Mitochondrial Proteins” in Cell Reports. The study found that P5A ATPase/CATP-8 can remove the mitochondrial signal anchored (SA) and tail-anchored (TA) that are incorrectly located on the ER, maintaining the specific “identity” of the ER.

 

 

The researchers used the mitochondrial SA/TA protein as the research object and conducted a large-scale screening in C. elegans and found that the catp-8 mutant caused the mitochondrial SA/TA protein to mislocate to the ER, and the two transmembrane proteins on the mitochondrial surface would not be affected. The fluorescence localization experiment found that CTP-8 was specifically localized on the ER, suggesting that it functions on the ER. At the same time, through light conversion and heat shock-induced expression experiments, the study found that CTP-8 can remove mitochondrial proteins that have been mislocated on the ER, and this process does not depend on the ERAD pathway. In order to study the importance of CTP-8 removal of the ER mislocalization protein to maintain the specific “identity” of the ER, the researchers found that the mitochondrial outer membrane proteins FIS-1 and MFF-2 were mislocalized to the ER in the catp-8 mutant, resulting the cleavage factor DRP-1 in mitochondria was mistakenly recruited to the ER, causing the ER to break. In addition, the research team found that CTP-8 affects the morphological development of nematode PVD neurons by regulating the level of the dendritic receptor protein DMA-1, suggesting that CTP-8 not only maintains the correct ER morphology by removing mitochondrial proteins that are mislocated to the ER. It also plays an important role in maintaining the normal physiological function of the ER. The study reported that the ER protein P5A ATPase/CATP-8 uses a monitoring mechanism to remove proteins that are incorrectly located on the ER, and its importance for maintaining the correct ER morphology and function.

 

 

Reference

Qing Qin, Ting Zhao, Wei Zou, et al. An Endoplasmic Reticulum ATPase Safeguards Endoplasmic Reticulum Identity by Removing Ectopically Localized Mitochondrial Proteins. Cell Report. Volume 33, Issue 6, 10 November 2020, 108363, https://doi.org/10.1016/j.celrep.2020.108363