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The metastatic lymph node-64 (MLN-64; MLN64; STARD3; CAB1) protein mediates endosomal cholesterol transport to mitochondria and the plasma membrane (Kennedy et al. 2014). It has been implicated in toxin-induced resistance. Down-regulation of MLN64 in Niemann-Pick C1 deficient cells decreased mitochondrial cholesterol content, suggesting that MLN64 functions independently of NPC1 (Balboa et al. 2017), and overexpression increases the mitochondrial cholesterol content and decreases the mitochondrial glutathione content, leading to mitochondrial dysfunction (Balboa et al. 2017). STARD3 is a key protein in the cholesterol movement in cancer cells (Asif et al. 2021). STARD3 is also a lutein- and zeaxanthin (carotenoid)-binding protein (Arunkumar et al. 2020).

MLN-64 of Homo sapiens (Q14849)

The Start1 protein (putative cholesterol transporter)
Start1 protein of Drosophila melanogaster (AAR19767)

STARD3 N-terminal-like protein, STARD3NL (MENTHO) of 234 aas and 3 TMSs.  MLN64 (metastatic lymph node 64) and MENTHO (MLN64 N-terminal homologue) are two late-endosomal proteins that share a conserved region of four transmembrane helices with three short intervening loops called the MENTAL domain (MLN64 N-terminal domain) (Alpy and Tomasetto 2006). This domain mediates MLN64 and MENTHO homo- and hetero-interactions, targets both proteins to late endosomes and binds cholesterol in vivo. In addition to the MENTAL domain, MLN64 contains a cholesterol-specific START domain [StAR (steroidogenic acute regulatory protein)-related lipid transfer domain]. The START domain is a protein module of approx. 210 residues that binds lipids, including sterols, and is present in 15 distinct proteins in mammals. Thus MLN64 and MENTHO define discrete cholesterol-containing subdomains within the membrane of late endosomes where they may function in cholesterol transport. The MENTAL domain might serve to maintain cholesterol at the membrane of late endosomes prior to its shuttle to cytoplasmic acceptor(s) through the START domain (Alpy and Tomasetto 2006).

STARD3NL of Homo sapiens