Issue 21, 2022

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.

Graphical abstract: Intramitochondrial co-assembly between ATP and nucleopeptides induces cancer cell apoptosis

Supplementary files

Article information

Article type
Edge Article
Submitted
19 Oct 2021
Accepted
11 Apr 2022
First published
22 Apr 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2022,13, 6197-6204

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

H. Choi, G. Park, E. Shin, S. W. Shin, B. Jana, S. Jin, S. Kim, H. Wang, S. K. Kwak, B. Xu and J. Ryu, Chem. Sci., 2022, 13, 6197 DOI: 10.1039/D1SC05738C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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