CALCOCO1, also known as calcium binding and coiled-coil domain 1, is an important autophagy receptor. It is involved in reticulophagy and Golgiphagy, which are key processes in maintaining cellular homeostasis. In reticulophagy, it helps degrade the tubular endoplasmic reticulum (ER) in response to proteotoxic and starvation-induced stress, and in Golgiphagy, it mediates the degradation of the Golgi apparatus during nutrient deprivation. These processes are crucial for regulating the quantity, volume, and integrity of organelles in the cell [1,2,3,4,5].

In cells, depletion of CALCOCO1 leads to impaired reticulophagy and Golgiphagy. For instance, lack of CALCOCO1 causes an expansion of the Golgi, as it fails to be degraded properly during starvation [1,5]. In the context of the ER, CALCOCO1-mediated ER-phagy is essential for maintaining proteostasis. Depletion of CALCOCO1 results in an expanded ER and inefficient basal autophagy flux [4].

In conclusion, CALCOCO1 plays a vital role in maintaining cellular homeostasis by mediating the selective autophagy of the ER and Golgi. The findings from loss-of-function studies, such as CALCOCO1 depletion in cells, have revealed its significance in organelle turnover. Understanding CALCOCO1 can potentially provide insights into diseases related to disrupted autophagy and organelle homeostasis.

References:

1. Nthiga, Thaddaeus Mutugi, Kumar Shrestha, Birendra, Lamark, Trond, Johansen, Terje. 2021. The soluble reticulophagy receptor CALCOCO1 is also a Golgiphagy receptor. In Autophagy, 17, 2051-2052. doi:10.1080/15548627.2021.1940610. https://pubmed.ncbi.nlm.nih.gov/34162311/

2. Kumar, Kamal, Chidambaram, Ravi, Parashar, Smriti, Ferro-Novick, Susan. 2024. RTN3L and CALCOCO1 function in parallel to maintain proteostasis in the endoplasmic reticulum. In Autophagy, 20, 2067-2075. doi:10.1080/15548627.2024.2353502. https://pubmed.ncbi.nlm.nih.gov/38818751/

3. Nthiga, Thaddaeus Mutugi, Shrestha, Birendra Kumar, Lamark, Trond, Johansen, Terje. 2020. CALCOCO1 is a soluble reticulophagy receptor. In Autophagy, 16, 1729-1731. doi:10.1080/15548627.2020.1797289. https://pubmed.ncbi.nlm.nih.gov/32684083/

4. Nthiga, Thaddaeus Mutugi, Kumar Shrestha, Birendra, Sjøttem, Eva, Lamark, Trond, Johansen, Terje. 2020. CALCOCO1 acts with VAMP-associated proteins to mediate ER-phagy. In The EMBO journal, 39, e103649. doi:10.15252/embj.2019103649. https://pubmed.ncbi.nlm.nih.gov/32525583/

5. Nthiga, Thaddaeus Mutugi, Shrestha, Birendra Kumar, Bruun, Jack-Ansgar, Lamark, Trond, Johansen, Terje. . Regulation of Golgi turnover by CALCOCO1-mediated selective autophagy. In The Journal of cell biology, 220, . doi:10.1083/jcb.202006128. https://pubmed.ncbi.nlm.nih.gov/33871553/