Table of contents

Volume 6, Issue 12, pp. 93 - 107, December 2022

Issue cover
Cover: This month in Cell Stress: Maintenance of axonal integrity by autophagy. Image shows cross-section of a nerve bundle. Image Credit: Fayette A Reynolds M.S. Public domain image via Berkshire Community College Bioscience Image Library. Image modified by Cell Stress. The cover is published under the CC BY 4.0 license. Enlarge issue cover

Research Articles

Autophagic degradation of CNS myelin maintains axon integrity

Niki Ktena, Stefanos Ioannis Kaplanis, Irina Kolotuev, Alexandros Georgilis, Emmanouela Kallergi, Vasiliki Stavroulaki, Vassiliki Nikoletopoulou, Maria Savvaki and Domna Karagogeos

page 93-107 | 10.15698/cst2022.12.274 | Full text | PDF | Abstract

(Macro)autophagy is a major lysosome-dependent degradation mechanism which engulfs, removes and recycles unwanted cytoplasmic material, including damaged organelles and toxic protein aggregates. Although a few studies implicate autophagy in CNS demyelinating pathologies, its role, particularly in mature oligodendrocytes and CNS myelin, remains poorly studied. Here, using both pharmacological and genetic inhibition of the autophagic machinery, we provide evidence that autophagy is an essential mechanism for oligodendrocyte maturation in vitro. Our study reveals that two core myelin proteins, namely proteolipid protein (PLP) and myelin basic protein (MBP) are incorporated into autophagosomes in oligodendrocytes, resulting in their degradation. Furthermore, we ablated atg5, a core gene of the autophagic machinery, specifically in myelinating glial cells in vivo by tamoxifen administration (plp-CreERT2; atg5 f/f) and showed that myelin maintenance is perturbed, leading to PLP accumulation. Significant morphological defects in myelin membrane such as decompaction accompanied with increased axonal degeneration are observed. As a result, the mice exhibit behavioral deficits. In summary, our data highlight that the maintenance of adult myelin homeostasis in the CNS requires the involvement of a fully functional autophagic machinery.

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