Mitofagia: una forma selectiva de autofagia que participa en la homeostasis de las células hematopoyéticas

CAVALIERE, V; KORNBLIHTT, L; BLANCO, GA

HEMATOLOGÍA

Sociedad Argentina de Hematología

Año: 2016 p. 216 - 223

2250-8309

AbstractAutophagyis a cellular process where cytoplasmic components and even whole organellesare sequestered in double-membrane vesicles (autophagosomes), and furtherdegraded upon fusion with lysosomes. It has an important role in the metabolicchanges that are needed to maintain cellular homeostasis. There are selectiveforms of autophagy where specific organelles are eliminated. This is the caseof mitophagy, a selective autophagy of mitochondria that are damaged or inexcess for the metabolic demand. In situations like hypoxia, mitochondrialrespiration can be deficient and produce damage because of the production ofreactive oxygen species (ROS). In this case, mitophagy operates as an adaptiveresponse, reducing the mitochondrial mass, while energy is then obtainedthrough glycolysis. In physiological circumstances like erythrocyte maturation,mitophagy ultimately eliminates the mitochondrial network. Hematopoietic stemcells (HSC) are adapted to a hypoxic environment, where energy is also derivedfrom glycolysis, reducing the production of ROS while supressing oxidativephosphorylation. This requires the HSC to keep high levels of mitophagy andautophagy. The genetic suppression of mitophagy in murine models increases ROSin HSC, loss of quiescence and self-renewal, inducing cytopenias andhematologic neoplasms. Mitophagy and autophagy can be also increased in hematologicneoplasms to resist in hostile environments such as hypoxia and nutrientdepletion, thus having importance in resistance to cytotoxic drugs.