Three-Way Effect of Cyanine Dye on the Structure and Function of Mitochondria

Abstract

Previously, we found that the cationic cyanine dye tri-S-C 4 (5) uncoupled mitochondrial oxidative phosphorylation by acting as an inducer of the mitochondrial permeability transition (PT). In the present study, the actions of cyanine dyes such as tri-S-C 4 (5) and tri-S-C 7 (5) on the mitochondrial structures and functions were further characterized. In the presence of inorganic phosphate (Pi), cyanine dyes were found to accelerate mitochondrial oxygen consumption that was partially sensitive to the PT inhibitor cyclosporin A (CsA). However, not only the CsAsensitive but also CsA-insensitive acceleration of mitochondrial respiration was induced by cyanine dyes; and both of them were found to be associated with the release of mitochondrial cytochrome c. On the contrary, in the absence of Pi, moderate acceleration of respiration was induced by cyanine dyes, but this respiratory effect was not associated with the induction of swelling or the release of mitochondrial cytochrome c. Thus, cyanine dyes were concluded to have 3 different effects on the mitochondrial functions depending on the Pi status.

Multiple effects of DiS‐C3(5) on mitochondrial structure and function

“…10 Unfortunately, no clear conclusion could be obtained, as mitochondria preswollen by DiS-C 3 (5) did not show any clear response upon the addition of poly(ethylene glycol) (data not shown). However, mitochondria treated with 50 lM DiS-C 3 (5) showed morphology different from that of the nontreated control (Fig.…”

“…These actions of cyanine dyes were attributable mainly to the results of induction of the mitochondrial PT [9,10]. Thus, acceleration of mitochondrial oxygen consumption by DiS-C 3 (5) was expected to be due to the induction of mitochondrial PT.…”

“…In our previous studies, cyanine dyes such as TriS‐C 4 (5) were found to accelerate mitochondrial oxygen consumption [6–8]. These actions of cyanine dyes were attributable mainly to the results of induction of the mitochondrial PT [9,10]. Thus, acceleration of mitochondrial oxygen consumption by DiS‐C 3 (5) was expected to be due to the induction of mitochondrial PT.…”

“…Furthermore, the accelerating effects of these cyanine dyes on the mitochondrial oxygen consumption were attributable mainly to the induction of the mitochondrial PT [9]. However, different from the classical PT induced by Ca , that induced by these cyanine dyes was only partially sensitive to a specific PT inhibitor, cyclosporin A (CsA) [9,10].On the contrary, a series of cyanine dyes used for measurement of mitochondrial membrane potential such as 3,3¢-diethyloxadicarbocyanine were reported to show inhibitory effects on complex I of the mitochondrial respiratory chain [11]. Furthermore, more recently, Scorrano et al reported that chloromethyltetramethylrosamine (Mitotracker Orang 2 e TM , Molecular Probes, Inc., Eugene, OR, USA), often used to monitor mitochondrial membrane potential in situ, showed both inhibitory effects on respiratory complex I and PT-inducing effects on isolated mitochondria [12].…”

“…Furthermore, the accelerating effects of these cyanine dyes on the mitochondrial oxygen consumption were attributable mainly to the induction of the mitochondrial PT [9]. However, different from the classical PT induced by Ca 2+ , that induced by these cyanine dyes was only partially sensitive to a specific PT inhibitor, cyclosporin A (CsA) [9,10].…”