title: Phototoxic effects of lysosome-associated genetically encoded photosensitizer KillerRed.
abstract: KillerRed is a unique phototoxic red fluorescent protein that can be used to induce local oxidative stress by green-orange light illumination. Here we studied phototoxicity of KillerRed targeted to cytoplasmic surface of lysosomes via fusion with Rab7, a small GTPase that is known to be attached to membranes of late endosomes and lysosomes. It was found that lysosome-associated KillerRed ensures efficient light-induced cell death similar to previously reported mitochondria- and plasma membrane-localized KillerRed. Inhibitory analysis demonstrated that lysosomal cathepsins play an important role in the manifestation of KillerRed-Rab7 phototoxicity. Time-lapse monitoring of cell morphology, membrane integrity, and nuclei shape allowed us to conclude that KillerRed-Rab7-mediated cell death occurs via necrosis at high light intensity or via apoptosis at lower light intensity. Potentially, KillerRed-Rab7 can be used as an optogenetic tool to direct target cell populations to either apoptosis or necrosis.
authors.affiliation: Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997, Moscow, Russia.
authors.forename: Ekaterina O
authors.initials: EO
authors.lastname: Serebrovskaya
authors.affiliation: Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997, Moscow, Russia.
authors.forename: Alina P
authors.initials: AP
authors.lastname: Ryumina
authors.affiliation: Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997, Moscow, Russia.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Boulina
authors.affiliation: Nizhny Novgorod State Medical Academy, 603005 Minin Sq., 10/1, 603005, Nizhny Novgorod, Russia.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Shirmanova
authors.affiliation: Nizhny Novgorod State Medical Academy, 603005 Minin Sq., 10/1, 603005, Nizhny Novgorod, Russia.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Zagaynova
authors.affiliation: Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997, Moscow, Russia.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Bogdanova
authors.affiliation: Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997, Moscow, RussiabNizhny Novgorod State Medical Academy, 603005 Minin Sq., 10/1, 603005, Nizhny Novgorod, Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Lukyanov
authors.affiliation: Russian Academy of Sciences, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16/10, 117997, Moscow, Russia.
authors.forename: Konstantin A
authors.initials: KA
authors.lastname: Lukyanov
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000737:chemistry; D008247:Lysosomes / Q000737:chemistry* / Q000378:metabolism; D009336:Necrosis; D018384:Oxidative Stress; D010778:Photochemotherapy / Q000295:instrumentation / Q000379:methods; D017319:Photosensitizing Agents / Q000737:chemistry*; D051381:Rats; D020691:rab GTP-Binding Proteins / Q000737:chemistry; D000090802:rab7 GTP-Binding Proteins; D000097573:Red Fluorescent Protein
chemical_list: D020558:GTP Phosphohydrolases; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D017319:Photosensitizing Agents; D020691:rab GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; D000097573:Red Fluorescent Protein; C508771:killer red protein, Anthomedusae; C000716463:rab7 GTP-binding proteins, human; C000716466:rab7 GTP-binding proteins, rat