Mitochondrial chaperone, TRAP1 as a potential pharmacological target to combat cancer metabolism

Publication date: Available online 25 October 2019Source: MitochondrionAuthor(s): Balaji Ramkumar, Shrikant P. Dharaskar, Mounika Guntipally, Khanderao Paithankar, Amere Subbarao SreedharAbstractThe stress response forms the most ancient defense system in living cells. Heat shock proteins (Hsps) are highly conserved across species and play major roles in mounting the stress response. The emerging information now suggests that Hsp90 family of chaperones display additional cellular roles contributing to diseases like cancer. For this reason, pharmacological targeting of Hsp90 has emerged as a novel antitumor strategy. However, its mitochondrial homologue TRAP1 has not been implicated in cancer with conclusive mechanistic insights. Since understanding the mutational spectrum of cancer cells indicates the outcome of the disease as well as treatment response, we examined mutational spectrum of TRAP1. Our in silico analyses of TRAP1 SNPs and CNVs correlated with the aggressive cancer phenotypes, and are found to be predominant over Hsp90 itself. The increased CNVs have been correlated with increased expression of TRAP1 in metastatic cancer cells, increased ATP production, and decreased oxygen consumption rate of mitochondria. Examining TRAP1 knockdown as well as over expression in metastatic cancer cells furthered our understanding that TRAP1 likely to facilitate the altered energy metabolism in the functional compromise of mitochondrial OXPHOS. Interestingly, the increased ATP lev...

Source: Mitochondrion - October 25, 2019 Category: Biochemistry Source Type: research