TY - JOUR
T1 - Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves
AU - Gomez-Sanchez, Jose A.
AU - Carty, Lucy
AU - Iruarrizaga-Lejarreta, Marta
AU - Palomo-Irigoyen, Marta
AU - Varela-Rey, Marta
AU - Griffith, Megan
AU - Hantke, Janina
AU - Macias-Camara, Nuria
AU - Azkargorta, Mikel
AU - Aurrekoetxea, Igor
AU - de Juan, Virginia Gutiérrez
AU - Jefferies, Harold B. J.
AU - Aspichueta, Patricia
AU - Elortza, Félix
AU - Aransay, Ana M.
AU - Martínez-Chantar, María L.
AU - Baas, Frank
AU - Mato, José M.
AU - Mirsky, Rhona
AU - Woodhoo, Ashwin
AU - Jessen, Kristján R.
PY - 2015
Y1 - 2015
N2 - Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell-mediated myelin digestion possible have not been established. We report that Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy. Autophagy was up-regulated by myelinating Schwann cells after nerve injury, myelin debris was present in autophagosomes, and pharmacological and genetic inhibition of autophagy impaired myelin clearance. Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury. We also present evidence that myelinophagy is defective in the injured central nervous system. These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease
AB - Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell-mediated myelin digestion possible have not been established. We report that Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy. Autophagy was up-regulated by myelinating Schwann cells after nerve injury, myelin debris was present in autophagosomes, and pharmacological and genetic inhibition of autophagy impaired myelin clearance. Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury. We also present evidence that myelinophagy is defective in the injured central nervous system. These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease
U2 - https://doi.org/10.1083/jcb.201503019
DO - https://doi.org/10.1083/jcb.201503019
M3 - Article
C2 - 26150392
SN - 0021-9525
VL - 210
SP - 153
EP - 168
JO - Journal of cell biology
JF - Journal of cell biology
IS - 1
ER -