Title

Mitochondrial-Localized Versus Cytosolic Intracellular CO-Releasing Organic PhotoCORMs: Evaluation of CO Effects Using Bioenergetics

Document Type

Article

Journal/Book Title

ACS Chemical Biology

Publication Date

8-17-2018

Publisher

American Chemical Society

Award Number

NIH 1R15GM124596-01, NSF, Division of Chemistry (CHEM) 1301092; Division of Chemistry (CHEM) 1429195; Utah Agricultural Experiment Station UTA-01178; Utah State University Office of Research and Graduate Studies Research Catalyst Grant; Utah State University Office of Research and Graduate Studies PDRF Fellowship

Funder

NIH; NSF, Division of Chemistry (CHEM); Utah Agricultural Experiment Station; Utah State University Office of Research and Graduate Studies

Volume

13

Issue

8

First Page

2220

Last Page

2228

Abstract

While interactions between carbon monoxide (CO) and mitochondria have been previously studied, the methods used to deliver CO (gas or CO-releasing metal carbonyl compounds) lack subcellular targeting and/or controlled delivery. Thus, the effective concentration needed to produce changes in mitochondrial bioenergetics is yet to be fully defined. To evaluate the influence of mitochondrial-targeted versusintracellularly released CO on mitochondrial oxygen consumption rates, we developed and characterized flavonol-based CO donor compounds that differ at their site of release. These molecules are metal-free, visible light triggered CO donors (photoCORMs) that quantitatively release CO and are trackable in cells via confocal microscopy. Our studies indicate that at a concentration of 10 μM, the mitochondrial-localized and cytosolic CO-releasing compounds are similarly effective in terms of decreasing ATP production, maximal respiration, and the reserve capacity of A549 cells. This concentration is the lowest to impart changes in mitochondrial bioenergetics for any CO-releasing molecule (CORM) reported to date. The results reported herein demonstrate the feasibility of using a structurally tunable organic photoCORM framework for comparative intracellular studies of the biological effects of carbon monoxide.

Comments

Free, publicly-accessible full text available through agency link on 2019-08-19.

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