Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes.
We sought to understand the relationship between reactive oxygen species (ROS) and the mitochondrial permeability transition (MPT) in cardiac myocytes based on the observation of increased ROS production at sites of spontaneously deenergized mitochondria. We devised a new model enabling incremental ROS accumulation in individual mitochondria in isolated cardiac myocytes via photoactivation of tetramethylrhodamine derivatives, which also served to report the mitochondrial transmembrane potential, DeltaPsi. This ROS accumulation reproducibly triggered abrupt (and sometimes reversible) mitochondrial depolarization. This phenomenon was ascribed to MPT induction because (a) bongkrekic acid prevented it and (b) mitochondria became permeable for calcein ( approximately 620 daltons) concurrently with depolarization. These photodynamically produced "triggering" ROS caused the MPT induction, as the ROS scavenger Trolox prevented it. The time required for triggering ROS to induce the MPT was dependent on intrinsic cellular ROS-scavenging redox mechanisms, particularly glutathione. MPT induction caused by triggering ROS coincided with a burst of mitochondrial ROS generation, as measured by dichlorofluorescein fluorescence, which we have termed mitochondrial "ROS-induced ROS release" (RIRR). This MPT induction/RIRR phenomenon in cardiac myocytes often occurred synchronously and reversibly among long chains of adjacent mitochondria demonstrating apparent cooperativity. The observed link between MPT and RIRR could be a fundamental phenomenon in mitochondrial and cell biology.
Zorov
D B
DB
Laboratory of Cardiovascular Sciences, Gerontology Research Center, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224-6825, USA.
Filburn
C R
CR
Klotz
L O
LO
Zweier
J L
JL
Sollott
S J
SJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D006321:Heart / Q000502:physiology*; D008929:Mitochondria, Heart / Q000378:metabolism / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010539:Permeability; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012995:Solubility; D013438:Sulfhydryl Compounds / Q000378:metabolism
D005456:Fluorescent Dyes; D011506:Proteins; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D002118:Calcium