Photodynamic Therapy: Apoptosis, Paraptosis and Autophagy

Photodynamic therapy (PDT) can elicit different cellular responses depending on sub -cellular sites of photodamage. Targeting lysosomes or mitochondria leadd to death by apoptosis, while ER photodamage can result in apoptosis and paraptosis. Autophagy is cytoprotective unless lysosomes are the primary target. We propose that the optimal targeting profile involves lysosomes, mitochondria and ER. Lysosomal phototoxicity is not limited by autophagy and can promote pro-apoptotic effects that magnify the lethality of mitochondrial photodamage. Targeting ER can be effective even in cells with an impaired apoptotic program since this death pathway is independent of apoptosis.