INVESTIGADORES
FADER KAISER Claudio Marcelo
artículos
Título:
HEMIN INDUCES MITOPHAGY IN A LEUKEMIC ERYTHROBLAST CELL LINE
Autor/es:
FADER CM; SALASSA BN; GROSSO RA; VERGARA AN; COLOMBO MI
Revista:
BIOLOGY OF THE CELL
Editorial:
PORTLAND PRESS LTD
Referencias:
Año: 2016
ISSN:
0248-4900
Resumen:
ABSTRACT Background Information: In eukaryotic cells, autophagy is considered as a lysosomal catabolic process which participates in the degradation of intracellular components in a vacuolar structure termed autolysosome. This pathway plays a significant role in the erythropoiesis process, contributing to the clearance of some organelles (such as mitochondria) that are not longer necessary in the mature red blood cells. Nevertheless, the role of autophagy in erythrocyte maturation has not been fully established.Results: Here we have demonstrated that hemin (a physiological erythroid maturation stimulator) is able to induce the expression of critical autophagic genes (i.e. Map1a1b (LC3), BECN1, Atg5) in an erythroleukemia cell type. We have also shown that hemin increased the size of autophagic vacuoles which were labeled with LC3 and the degradative lysosomal marker DQ-BSA. In addition, we have determined by Western blot a rise in the lipidated form of the autophagic protein LC3 (i.e. LC3-II) upon hemin treatment. Moreover, we provide evidences that hemin induces mitochondrial membrane depolarization and that mitochondria sequestration by autophagy requires the active form of the NIX protein. Conclusions: We have found that the physiological erythroid maturation stimulator hemin is able to induce mitophagy in K562 cells, and that the autophagy adaptor NIX is necessary for mitophagy progression. K562 cells have been used as a relevant model to determine the possible therapeutic role of new differentiating compounds. On the other hand, it has been proposed that autophagy induction is a feasible new therapeutic key in fighting cancer. Our results suggest that hemin is favoring erythroid maturation by inducing an autophagic response in K562 cells, being a possible therapeutic candidate that may help in the chronic myelogenous leukemia (CML) treatment.
