2024-03-29T02:02:56Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1496472021-12-27T15:34:45Zcom_10261_86com_10261_1col_10261_339
2017-05-11T11:41:44Z
urn:hdl:10261/149647
Programmed mitophagy is essential for the glycolytic switch during cell differentiation
Esteban-Martínez, Lorena
Sierra-Filardi, Elena
Boya, Patricia
Ministerio de Economía y Competitividad (España)
Consejo Superior de Investigaciones Científicas (España)
Fundación BBVA
Asociación Española Contra el Cáncer
BNIP3L/NIX
Hypoxia
Macrophages
Metabolic reprogramming
Retinal ganglion cells
19 p.-8 fig. Esteban-Martínez, Lorena et al.
Retinal ganglion cells (RGCs) are the sole projecting neurons of the retina and their axons form the optic nerve. Here, we show that embryogenesis-associated mouse RGC differentiation depends on mitophagy, the programmed autophagic clearance of mitochondria.The elimination of mitochondria during RGC differentiation was coupled to a metabolic shift with increased lactate production and elevated expression of glycolytic enzymes at the mRNA level.Pharmacological and genetic inhibition of either mitophagy or glycolysis consistently inhibited RGC differentiation. Local hypoxia triggered expression of the mitophagy regulator BCL2/adenovirus E1B 19-kDa-interacting protein 3-like (BNIP3L, best known as NIX)at peak RGC differentiation. Retinas from NIX-deficient mice displayed increased mitochondrial mass, reduced expression of
glycolytic enzymes and decreased neuronal differentiation.Similarly, we provide evidence that NIX-dependent mitophagy contributes to mitochondrial elimination during macrophage polarization towards the proinflammatory and more glycolytic M1 phenotype, but not to M2 macrophage differentiation, which primarily relies on oxidative phosphorylation. In summary, developmentally controlled mitophagy promotes a metabolic switch towards glycolysis, which in turn contributes to cellular differentiation
in several distinct developmental contexts.
2017-05-11T11:41:44Z
2017-05-11T11:41:44Z
2017-05-02
artículo
The EMBO Journal e201695916 (2017)
0261-4189
http://hdl.handle.net/10261/149647
10.15252/embj.201695916
1460-2075
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100003339
http://dx.doi.org/10.13039/100007406
28465321
eng
http://dx.doi.org/10.15252/embj.201695916
Sí
openAccess
Nature Publishing Group