Intramitochondrial co-assembly between ATP and nucleopeptides induces cancer cell apoptosis.

ABSTRACT: Mitochondria are essential intracellular organelles involved in many cellular processes, especially adenosine triphosphate (ATP) production. Since cancer cells require high ATP levels for proliferation, ATP elimination can be a unique target for cancer growth inhibition. We describe a newly developed mitochondria-targeting nucleopeptide (MNP) that sequesters ATP by self-assembling with ATP inside mitochondria. MNP interacts strongly with ATP through electrostatic and hydrogen bonding interactions. MNP exhibits higher binding affinity for ATP (-637.5 kJ mol^-1) than for adenosine diphosphate (ADP) (-578.2 kJ mol^-1). To improve anticancer efficacy, the small-sized MNP/ADP complex formed large assemblies with ATP inside cancer cell mitochondria. ATP sequestration and formation of large assemblies of the MNP/ADP-ATP complex inside mitochondria caused physical stress by large structures and metabolic disorders in cancer cells, leading to apoptosis. This work illustrates a facile approach to developing cancer therapeutics that relies on molecular assemblies.

SUBMITTER: Choi H 

PROVIDER: S-EPMC9159100 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature