Medicine and Health Sciences Commons^™

Mitochondrial Unfolded Protein Response Regulator Atf5 In Mitochondrial Targeted Therapies In Aml, Ran Zhao

Dissertations & Theses (Open Access)

Mitochondrial unfolded protein response (UPR^mt) is an adaptive transcriptional response induced by damaged proteins accumulated in mitochondria. UPR^mt signaling involves induction of mitochondrial specific chaperones and proteases such as HSP60, LonP1 and ClpP, aiding in the restoration of mitochondrial protein pool homeostasis. However, the cell-protective roles of UPR^mt in the context of mitochondrial stress-induced cell death in AML has not been well explored. We demonstrate that AML cells are susceptible to mitochondrial targeted agents such as ONC201, an agonist of the mitochondrial protease ClpP, and gamitrinib, an inhibitor of mitochondrial chaperone TRAP1, however, these agents also …