Collapsin Response Mediator Protein 5 (CRMP5) Induces Mitophagy Thereby Regulating Mitochondrion Numbers in Dendrites. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2013

Collapsin Response Mediator Protein 5 (CRMP5) Induces Mitophagy Thereby Regulating Mitochondrion Numbers in Dendrites.

Résumé

: Degradation of damaged mitochondria by mitophagy is an essential process to ensure cell homeostasis. Because neurons, with a high-energy demand, are particularly dependent on the mitochondrial dynamics, mitophagy represents a key mechanism ensuring a correct neuronal function. Collapsin response mediator proteins 5 (CRMP5) belongs to a family of cytosolic proteins involved in axon guidance and neurite outgrowth signaling during neural development. CRMP5, highly expressed during brain development, plays an important role in the regulation of neuronal polarity by inhibiting dendrite outgrowth at early developmental stages. Here, we demonstrate that CRMP5 is present, in vivo, in brain mitochondria, and is targeted to the inner mitochondrial membrane. The mitochondrial localization of CRMP5 induces mitophagy; CRMP5 over-expression triggers a drastic change in mitochondrial morphology, increases the number of lysosomes and double-membrane vesicles termed autophagosomes, and enhances the occurrence of microtubule-associated protein 1 light chain 3 (LC3) at mitochondrial level. Moreover, LC3 lipidated form, LC3-II, triggering autophagy by insertion into autophagosomes, enhances indicating mitophagy initiation. Lysosomal marker translocates at the mitochondrial level suggesting autophagosome-lysosome fusion, and induces the reduction of mitochondrial content via lysosomal degradation. We show that during early developmental stages, the strong expression of endogenous CRMP5, inhibiting dendrite growth, correlates with a decrease of mitochondrial content. On the opposite, the knockdown or the decrease of CRMP5 expression at later stages, both enhances mitochondrion numbers in cultured neurons, suggesting that CRMP5 modulates these numbers. Our study elucidates a novel regulatory mechanism that utilizes CRMP5-induced mitophagy to orchestrate proper dendrite outgrowth and neuronal function.

Dates et versions

hal-00917349 , version 1 (11-12-2013)

Identifiants

Citer

Sébastien Brot, Carole Auger, Rabia Bentata, Véronique Rogemond, Stéphane Ménigoz, et al.. Collapsin Response Mediator Protein 5 (CRMP5) Induces Mitophagy Thereby Regulating Mitochondrion Numbers in Dendrites.. Journal of Biological Chemistry, 2013, 289, pp.2261-2276. ⟨10.1074/jbc.M113.490862⟩. ⟨hal-00917349⟩
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