STARD3, short for StAR-related lipid transfer protein domain 3, is a member of the START family. It is a sterol-binding protein that plays a crucial role in lipid transfer, especially in non-vesicular cholesterol transportation within the cell. It creates endoplasmic reticulum (ER)-endosome contact sites and mediates the transport of cholesterol from the endoplasmic reticulum to endosomes, thus modulating cellular cholesterol repartition [1,4]. Cholesterol metabolism is an essential pathway in cells, and STARD3's function in this pathway is of great biological importance. Genetic models could be valuable for further studying its function.

In diabetes-related research, upregulation of STARD3 under diabetes and hyperglycemia increases cholesterol transport from the late endosomal/lysosomal to mitochondria in podocytes, leading to mitochondrial cholesterol accumulation and cell injury. Conversely, down-regulating STARD3 expression attenuated mitochondrial cholesterol accumulation and improved mitochondrial homeostasis, suggesting targeting STARD3 could be a potential therapeutic strategy for diabetes-induced podocyte injury [3]. In HER2-positive breast cancer, a retrospective study on 112 patients found that STARD3-negative score was associated with the absence of pathological complete response after neoadjuvant systemic treatment, indicating STARD3 overexpression status determination on initial biopsies may have added value in patient management [2].

In conclusion, STARD3 is a key protein in cholesterol movement within cells. Model-based research, such as the studies on diabetes-induced podocyte injury and HER2-positive breast cancer, reveals its significance in disease-related biological processes. These findings suggest that STARD3 could be a potential target for therapies in diabetes-related kidney diseases and HER2-positive breast cancer, providing insights into disease mechanisms and treatment strategies.

References:

1. Wilhelm, Léa P, Tomasetto, Catherine, Alpy, Fabien. . Touché! STARD3 and STARD3NL tether the ER to endosomes. In Biochemical Society transactions, 44, 493-8. doi:10.1042/BST20150269. https://pubmed.ncbi.nlm.nih.gov/27068960/

2. Lodi, Massimo, Voilquin, Laetitia, Alpy, Fabien, Chenard, Marie-Pierrette, Tomasetto, Catherine-Laure. 2023. STARD3: A New Biomarker in HER2-Positive Breast Cancer. In Cancers, 15, . doi:10.3390/cancers15020362. https://pubmed.ncbi.nlm.nih.gov/36672312/

3. Hu, Jijia, Zhu, Zijing, Zhang, Zongwei, Hu, Hongtu, Yang, Qian. 2024. Blockade of STARD3-mediated cholesterol transport alleviates diabetes-induced podocyte injury by reducing mitochondrial cholesterol accumulation. In Life sciences, 349, 122722. doi:10.1016/j.lfs.2024.122722. https://pubmed.ncbi.nlm.nih.gov/38754814/

4. Wilhelm, Léa P, Wendling, Corinne, Védie, Benoît, Drin, Guillaume, Alpy, Fabien. 2017. STARD3 mediates endoplasmic reticulum-to-endosome cholesterol transport at membrane contact sites. In The EMBO journal, 36, 1412-1433. doi:10.15252/embj.201695917. https://pubmed.ncbi.nlm.nih.gov/28377464/