Volumen: 20 # Number : 2
Publication Date : Mayo - Agosto Year: 2016
Mitophagy: a selective form of autophagy that
participates in hemopoyetic cell homeostasis
Authors: Kornblihtt LI, Cavaliere V, Blanco GA
Abstract: Autophagy is a cellular process where cytoplasmic
components and even whole organelles are sequestered
in double-membrane vesicles (autophagosomes),
and further degraded upon fusion with lysosomes.
It has an important role in the metabolic changes
that are needed to maintain cellular homeostasis.
There are selective forms of autophagy where specific
organelles are eliminated. This is the case of mitophagy,
a selective autophagy of mitochondria that
are damaged or in excess for the metabolic demand.
In situations like hypoxia, mitochondrial respiration
can be deficient and produce damage because of the
production of reactive oxygen species (ROS). In this
case, mitophagy operates as an adaptive response,
reducing the mitochondrial mass, while energy is
then obtained through glycolysis.
In physiological circumstances like erythrocyte
maturation, mitophagy ultimately eliminates the
mitochondrial network. Hematopoietic stem cells
(HSC) are adapted to a hypoxic environment, where
energy is also derived from glycolysis, reducing the
production of ROS while supressing oxidative phosphorylation.
This requires the HSC to keep high levels
of mitophagy and autophagy. The genetic suppression
of mitophagy in murine models increases
ROS in HSC, loss of quiescence and self-renewal,
inducing cytopenias and hematologic neoplasms.
Mitophagy and autophagy can be also increased in
hematologic neoplasms to resist in hostile environments
such as hypoxia and nutrient depletion, thus
having importance in resistance to cytotoxic drugs.
Key words: Autophagy and mitophagy,
BNIP3,
Hematopoiesis and erythropoiesis,
Cellular homeostasis,
Resistance to cytotoxic drugs
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