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

      1 , 2 , 1 , 1 , 2
      ACS Chemical Biology
      American Chemical Society (ACS)

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          Abstract

          <p class="first" id="P1">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 versus intracellularly-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. </p>

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          Author and article information

          Journal
          ACS Chemical Biology
          ACS Chem. Biol.
          American Chemical Society (ACS)
          1554-8929
          1554-8937
          July 06 2018
          August 17 2018
          June 22 2018
          August 17 2018
          : 13
          : 8
          : 2220-2228
          Affiliations
          [1 ]Department of Chemistry and Biochemistry, Utah State University, Logan, Utah 84322-0300, United States
          [2 ]Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan, Utah 84322-4815, United States
          Article
          10.1021/acschembio.8b00387
          6117112
          29932318
          6e3fe007-412f-45f8-a911-8cd8478cc52f
          © 2018
          History

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