Dataset Information

Analysing the mechanism of mitochondrial oxidation-induced cell death using a multifunctional iridium(III) photosensitiser.

ABSTRACT: Mitochondrial oxidation-induced cell death, a physiological process triggered by various cancer therapeutics to induce oxidative stress on tumours, has been challenging to investigate owing to the difficulties in generating mitochondria-specific oxidative stress and monitoring mitochondrial responses simultaneously. Accordingly, to the best of our knowledge, the relationship between mitochondrial protein oxidation via oxidative stress and the subsequent cell death-related biological phenomena has not been defined. Here, we developed a multifunctional iridium(III) photosensitiser, Ir-OA, capable of inducing substantial mitochondrial oxidative stress and monitoring the corresponding change in viscosity, polarity, and morphology. Photoactivation of Ir-OA triggers chemical modifications in mitochondrial protein-crosslinking and oxidation (i.e., oxidative phosphorylation complexes and channel and translocase proteins), leading to microenvironment changes, such as increased microviscosity and depolarisation. These changes are strongly related to cell death by inducing mitochondrial swelling with excessive fission and fusion. We suggest a potential mechanism from mitochondrial oxidative stress to cell death based on proteomic analyses and phenomenological observations.

SUBMITTER: Lee C

PROVIDER: S-EPMC7782791 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Analysing the mechanism of mitochondrial oxidation-induced cell death using a multifunctional iridium(III) photosensitiser.

Lee Chaiheon C Nam Jung Seung JS Lee Chae Gyu CG Park Mingyu M Yoo Chang-Mo CM Rhee Hyun-Woo HW Seo Jeong Kon JK Kwon Tae-Hyuk TH

Nature communications 20210104 1

Mitochondrial oxidation-induced cell death, a physiological process triggered by various cancer therapeutics to induce oxidative stress on tumours, has been challenging to investigate owing to the difficulties in generating mitochondria-specific oxidative stress and monitoring mitochondrial responses simultaneously. Accordingly, to the best of our knowledge, the relationship between mitochondrial protein oxidation via oxidative stress and the subsequent cell death-related biological phenomena ha ...[more]

PMID: 33397915

Similar Datasets

Project description:Background and aimIridium (Ir)-based complex is a potential antitumor ingredient, but its poor physicochemical properties such as hydrophobicity and low biocompatibility hamper further application. Liposome provides a potential delivery approach for improving the poor physicochemical property and reducing the side effects of antitumor drug. In this study, we aimed at incorporating Ir ([Ir(ppy)2(BTCP)]PF6) into liposomes to enhance the biocompatibility and sustained release of Ir for intravenous administration and to elucidate the mechanism in A549 cells.Materials and methodsIr-loaded PEGylated liposomes (Lipo-Ir) were formulated by thin-film dispersion and ultrasonic method. Morphology, size distribution, and zeta potential of Lipo-Ir were examined by transmission electron microscopy (TEM) and Zetasizer. The released profile and biocompatibility were investigated by dialysis method and hemolysis test, respectively. Additionally, the cytotoxic activity and mechanism of Lipo-Ir and Ir inducing apoptosis in A549 cells were evaluated.ResultsLipo-Ir can keep sustained release, excellent biocompatibility, and physical stability. The average particle size, polydispersity index, zeta potential, encapsulation efficiency, and drug loading are 112.57±1.15 nm, 0.19±0.02, -10.66±0.61 mV, 94.71%±3.21%, and 4.71%±0.41%, respectively. 3-(4,5-dimethylthiazole)-2,5-diphenltetraazolium bromide (MTT) assay show that Lipo-Ir and Ir display high cytotoxicity against selected cancer cells. Furthermore, the apoptotic features of morphology, depolarization of mitochondrial membrane potential, increase in the reactive oxygen species (ROS) levels, and disorder of Ca2+ homeostasis are observed after treating A549 cells with Ir and Lipo-Ir. Besides, Lipo-Ir can arrest the cell growth in G0/G1 phase.ConclusionThe studies demonstrate that Lipo-Ir can trigger apoptosis in A549 cells via ROS-mediated mitochondrial dysfunctions, and the biocompatible and sustained Lipo-Ir will be a promising drug delivery system.

Dataset Information

Analysing the mechanism of mitochondrial oxidation-induced cell death using a multifunctional iridium(III) photosensitiser.

Publications

Analysing the mechanism of mitochondrial oxidation-induced cell death using a multifunctional iridium(III) photosensitiser.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets