Mitochondrial fusion protein optic atrophy (OPA)1 is upregulated in AML patients with adverse mutations and correlates with poor prognosis.<h4>Method</h4>This study investigated targeting OPA1 with TMQ0153, a tetrahydrobenzimidazole derivative, to disrupt mitochondrial metabolism and dynamics as a novel therapeutic approach to overcome treatment resistance. This evidence concerns the gene OPA1 and acute myeloid leukemia.