Mitophagy as a Regulator of Metabolism and Cell Differentiation Beatriz Villarejo-Zori, Patricia Boya Centro de Investigaciones Biológicas, CIB-CSIC, Madrid, Spain Autophagy is a degradative pathway that mediates the degradation and recycling of cellular components inside lysosomes. These components can include whole organelles, such as mitochondria, in which case the process is known as mitophagy. Mitophagy is the only known pathway that can eliminate entire mitochondria, and defects in this process are implicated in diseases as neurodegenerative conditions as well as during aging-realted diseases. We have demonstrated that mitophagy by controlling mitocondrial number regulates a metabolic shift towards glycolysis in several cell types such as neurons and macrophages. More importantly, we show that mouse neuronal differentiation depends on mitophagy. The elimination of mitochondria during retinal ganglion cell differentiation is 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 neuronal differentiation. We are also exploring how mitophagy defects are associated with age-related diseases such as glaucoma and Parkinson disease and whether manipulation of this process could represent new avenues for degenerative and age-related diseases.
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