Your browser doesn't support javascript.
loading
Knockdown of BNIP3L or SQSTM1 alters cellular response to mitochondria target drugs.
Rodrigo, Rowena; Mendis, Nilmini; Ibrahim, Medhat; Ma, Christina; Kreinin, Elena; Roma, Alessia; Berg, Spencer; Blay, Jonathan; Spagnuolo, Paul A.
Afiliación
  • Rodrigo R; a School of Pharmacy , University of Waterloo , Kitchener , Canada.
  • Mendis N; b Department of Food Science , University of Guelph , Guelph , Canada.
  • Ibrahim M; b Department of Food Science , University of Guelph , Guelph , Canada.
  • Ma C; a School of Pharmacy , University of Waterloo , Kitchener , Canada.
  • Kreinin E; a School of Pharmacy , University of Waterloo , Kitchener , Canada.
  • Roma A; b Department of Food Science , University of Guelph , Guelph , Canada.
  • Berg S; a School of Pharmacy , University of Waterloo , Kitchener , Canada.
  • Blay J; a School of Pharmacy , University of Waterloo , Kitchener , Canada.
  • Spagnuolo PA; a School of Pharmacy , University of Waterloo , Kitchener , Canada.
Autophagy ; 15(5): 900-907, 2019 05.
Article en En | MEDLINE | ID: mdl-30563411
Macroautophagy/autophagy, a pathway by which cellular components are sequestered and degraded in response to homeostatic and cell stress-related signals, is required to preserve hematopoietic stem and progenitor cell function. Loss of chromosomal regions carrying autophagy genes and decreased autophagy gene expression are characteristic of acute myeloid leukemia (AML) cells. Deficiency of autophagy proteins is also linked to an altered AML metabolic profile; altered metabolism has recently emerged as a potential druggable target in AML. Here, we sought to understand the mitochondria-specific changes that occur in leukemia cells after knockdown of BNIP3L/Nix or SQSTM1/p62, which are two autophagy genes involved in mitochondrial clearance and are downregulated in primary AML cells. Mitochondrial function, as measured by changes in endogenous levels of reactive oxygen species (ROS) and mitochondrial membrane potential, was altered in leukemia cells deficient in these autophagy genes. Further, these AML cells were increasingly sensitive to mitochondria-targeting drugs while displaying little change in sensitivity to DNA-targeting agents. These findings suggest that BNIP3L or SQSTM1 may be useful prognostic markers to identify AML patients suitable for mitochondria-targeted therapies. Abbreviations: AML: acute myeloid leukemia; DHE: dihydroethidium; mtDNA: mitochondrial DNA; NAO: 10-N-nonyl acridine orange; PD: population doubling; R123: rhodamine 123; ROS: reactive oxygen species; TRC: transduced scramble controls.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas / Proteínas Supresoras de Tumor / ARN Interferente Pequeño / Proteína Sequestosoma-1 / Proteínas de la Membrana / Mitocondrias / Antineoplásicos / Antioxidantes Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Autophagy Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Proto-Oncogénicas / Proteínas Supresoras de Tumor / ARN Interferente Pequeño / Proteína Sequestosoma-1 / Proteínas de la Membrana / Mitocondrias / Antineoplásicos / Antioxidantes Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Autophagy Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos