Plin3, also known as perilipin 3, is a lipid droplet-associated protein belonging to the perilipin family. It plays essential roles in lipid metabolism, especially in processes related to lipid droplet degradation and lipophagy. The mTORC1-Plin3 pathway is crucial for activating lipophagy, and Plin3 may function as a docking protein or be involved in autophagosome formation to initiate this process [2]. It is also associated with various disease-related pathways, such as those in prostate cancer, non-alcoholic fatty liver disease (NAFLD), and alcoholic liver disease (ALD) [1,2,3]. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying its functions.

In prostate cancer, the acyl-CoA synthetase short chain family member 3 (ACSS3) represses cancer progression by downregulating Plin3, reducing lipid droplet (LD) deposits, promoting apoptosis, and inhibiting de novo intratumoral androgen synthesis [1]. In NAFLD, the mTORC1-Plin3 pathway activates lipophagy, protecting against hepatosteatosis. Plin3 knockdown abolishes lipophagy activation, suggesting its essential role in this process [2]. In alcoholic liver injury, Plin3 protects against injury by facilitating lipid export from the endoplasmic reticulum. Plin3 knockdown increases cellular sensitivity to alcohol-induced apoptosis, ER stress, and inflammatory cytokine release [3].

In conclusion, Plin3 is vital for lipid metabolism and lipophagy. Model-based research, especially KO/CKO mouse models, has revealed its significance in diseases like prostate cancer, NAFLD, and alcoholic liver disease. Understanding Plin3's functions provides potential therapeutic targets for these disease areas.

References:

1. Zhou, Lijie, Song, Zhengshuai, Hu, Junyi, Yang, Xiong, Chen, Ke. 2021. ACSS3 represses prostate cancer progression through downregulating lipid droplet-associated protein PLIN3. In Theranostics, 11, 841-860. doi:10.7150/thno.49384. https://pubmed.ncbi.nlm.nih.gov/33391508/

2. Garcia-Macia, Marina, Santos-Ledo, Adrián, Leslie, Jack, Oakley, Fiona, Mann, Derek A. 2021. A Mammalian Target of Rapamycin-Perilipin 3 (mTORC1-Plin3) Pathway is essential to Activate Lipophagy and Protects Against Hepatosteatosis. In Hepatology (Baltimore, Md.), 74, 3441-3459. doi:10.1002/hep.32048. https://pubmed.ncbi.nlm.nih.gov/34233024/

3. Gu, Yu, Yang, Ying, Cao, Xiangmei, Xiao, Liming, Ye, Jing. 2019. Plin3 protects against alcoholic liver injury by facilitating lipid export from the endoplasmic reticulum. In Journal of cellular biochemistry, 120, 16075-16087. doi:10.1002/jcb.28889. https://pubmed.ncbi.nlm.nih.gov/31119787/