Photosensitization of intact heart mitochondria by the phthalocyanine Pc 4: Correlation of structural and functional deficits with cytochrome c release.
Singlet oxygen is produced by the absorption of red light by the phthalocyanine dye Pc 4, followed by energy transfer to dissolved triplet oxygen. Mitochondria preincubated with Pc 4 were illuminated by red light and the damage to mitochondrial structure and function by the generated singlet oxygen was studied. At early illumination times (3-5 min of red light exposure), State 3 respiration was inhibited (50%), whereas State 4 activity increased, resulting in effectively complete uncoupling. Individual complex activities were measured and only complex IV activity was significantly reduced and exhibited a dose response, whereas the activities of electron transport complexes I, II, and III were not significantly affected. Cytochrome c release was an increasing function of irradiation time, with 30% being released after 5 min of illumination. Mitochondrial expansion along with changes in the structure of the cristae were observed by transmission electron microscopy after 5 min of irradiation, with an increase in large vacuoles and membrane rupture occurring after more extensive exposures.
Kim
Junhwan
J
Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Fujioka
Hisashi
H
Oleinick
Nancy L
NL
Anderson
Vernon E
VE
D000818:Animals; D045304:Cytochromes c / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008027:Light; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects* / Q000648:ultrastructure; D010085:Oxidative Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D017319:Photosensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism
D007211:Indoles; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; C107448:phthalocyanine Pc 4; D045304:Cytochromes c