Prophylaxis of mitochondrial dysfunction caused by cellular decompression from hyperbaric exposure

• Published in: Mitochondrion Vol. 52; pp. 8 - 19
• Main Authors: Ranganathan, Abhay, Owiredu, Shawn, Jang, David H., Eckmann, David M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2020
• Subjects: Bioenergetics; Decompression; Intermembrane potential; Microscopy; Mitochondria; Motility; Perinuclear; Respiration; Mitochondria; Motility; Bioenergetics; Intermembrane potential; Microscopy; Perinuclear; Decompression; Respiration
• ISSN: 1567-7249; 1872-8278
• DOI: 10.1016/j.mito.2020.02.002

•Vascular smooth muscle cells are decompressed from hyperbaric exposure.•Mitochondrial motility and respiratory function are affected.•A succinate prodrug provides partial prophylaxis from these effects. Mitochondrial dysfunction occurring in response to cellular perturbations can include altered mitochondrial motility and bioenergetic function having intracellular heterogeneity. Exogenous mitochondrial directed therapy may correct these dysfunctions. Using in vitro approaches, we find that cell perturbations induced by rapid decompression from hyperbaric conditions with specific gas exposures has differential effects on mitochondrial motility, inner membrane potential, cellular respiration, reactive oxygen species production, impaired maintenance of cell shape and altered intracellular distribution of bioenergetic capacity in perinuclear and cell peripheral domains. Addition of a first-generation cell-permeable succinate prodrug to support mitochondrial function has positive overall effects in blunting the resultant bioenergy responses. Our results with this model of perturbed cell function induced by rapid decompression indicate that alterations in bioenergetic state are partitioned within the cell, as directly assessed by a combination of mitochondrial respiration and dynamics measurements. Reductions in the observed level of dysfunction produced can be achieved with application of the cell-permeable succinate prodrug.