Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Parallel damage in mitochondria and lysosomes is an efficient way to photoinduce cell death

Texto completo
Autor(es):
Mostrar menos -
Martins, Waleska K. [1, 2] ; Santos, Nayra Fernandes [1] ; Rocha, Cleidiane de Sousa [1, 2] ; Bacellar, Isabel O. L. [1] ; Tsubone, Tayana Mazin [1] ; Viotto, Ana Claudia [1] ; Matsukuma, Adriana Yamaguti [1] ; Abrantes, Aline B. de P. [1] ; Siani, Paulo [3] ; Dias, Luis Gustavo [3] ; Baptista, Mauricio S. [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Bioquim, Inst Quim, Sao Paulo - Brazil
[2] Univ Anhanguera Sao Paulo, Programa Posgrad Stricto Sensue Pesquisa, Sao Paulo - Brazil
[3] Univ Sao Paulo, Dept Quim, FFCLRP, Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: AUTOPHAGY; v. 15, n. 2, p. 259-279, FEB 1 2019.
Citações Web of Science: 0
Resumo

Cells challenged by photosensitized oxidations face strong redox stresses and rely on autophagy to either survive or die. However, the use of macroautophagy/autophagy to improve the efficiency of photosensitizers, in terms of inducing cell death, remains unexplored. Here, we addressed the concept that a parallel damage in the membranes of mitochondria and lysosomes leads to a scenario of autophagy malfunction that can greatly improve the efficiency of the photosensitizer to cause cell death. Specific damage to these organelles was induced by irradiation of cells pretreated with 2 phenothiazinium salts, methylene blue (MB) and 1,9-dimethyl methylene blue (DMMB). At a low concentration level (10 nM), only DMMB could induce mitochondrial damage, leading to mitophagy activation, which did not progress to completion because of the parallel damage in lysosome, triggering cell death. MB-induced photodamage was perceived almost instantaneously after irradiation, in response to a massive and nonspecific oxidative stress at a higher concentration range (2 mu M). We showed that the parallel damage in mitochondria and lysosomes activates and inhibits mitophagy, leading to a late and more efficient cell death, offering significant advantage (2 orders of magnitude) over photosensitizers that cause unspecific oxidative stress. We are confident that this concept can be used to develop better light-activated drugs. (AU)

Processo FAPESP: 13/07937-8 - Redoxoma
Beneficiário:Ohara Augusto
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 16/07642-6 - A ativação/inibição da autofagia pelos triterpenóides e o impacto da interação em membranas: implicações terapêuticas antitumorais
Beneficiário:Waleska Kerllen Martins Gardesani
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 12/50680-5 - Fotossensibilização nas ciências da vida
Beneficiário:Mauricio da Silva Baptista
Linha de fomento: Auxílio à Pesquisa - Temático