Apoptosis, autophagy and cell cycle arrest following photodamage to mitochondrial interior.
Cell death induced by oxidative insult targeted to mitochondrial interior of A431 cells was investigated. For stimulated production of ROS in the inner space of mitochondria, safranin-mediated photodynamic treatment (PDT) was employed. Another photosensitizer, mTHPC, which diffusely localizes to cellular membranes, was used for comparison. Cell response to the oxidative insult in mitochondrial interior was different from the response to the photodamage produced in cellular membranes. Autophagy and apoptotic features of cell death in response to mTHPC-PDT was observed in a wide range of PDT doses. Cell response to the oxidative stress in mitochondrial interior was dose-dependent. Damage up to CD50 did not reveal hallmarks of dead cells. At intermediate damage (CD50), cells manifested enhanced autophagy and reduced population of S-phase, but not apoptosis. Severe damage (beyond CD70) induced apoptosis following release of cytochrome c and caspase activation, in addition to autophagy and cell cycle arrest.
Sasnauskiene
Ausra
A
Department of Biochemistry and Biophysics, Vilnius University, Ciurlionio 21/27, Vilnius, Lithuania.
Kadziauskas
Jurgis
J
Vezelyte
Neringa
N
Jonusiene
Violeta
V
Kirveliene
Vida
V
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002950:Citrate (si)-Synthase / Q000187:drug effects / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D007202:Indicators and Reagents / Q000494:pharmacology; D008652:Mesoporphyrins / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D010619:Phenazines / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007202:Indicators and Reagents; D008652:Mesoporphyrins; D010619:Phenazines; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D045304:Cytochromes c; D002950:Citrate (si)-Synthase; D053148:Caspase 3; C072269:temoporfin; C009195:safranine T