Ultrastructural analysis of the membrane origin for autophagy

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Neurons in brains of cathepsin D-deficient (CD-/-) mice, a murine model for neuronal ceroid lipofuscinoses (NCLs), possess abundant autophagosomes and granular osmiophilic deposits (GRODs),which are often found in nascent autophagosomes. In addition to immunocytochemical localization of LC3 and ubiquitin in, p62 and Nbr1, both of which can interact with both ubiquitin and LC3, were found to be also localized on the membrane of GRODs. Moreover, these molecules were present in the same granules of the neurons. The data indicate that ubiquitin and p62 and/or Nbr1 on the membrane of GRODs may serve as a signal of autophagy that contributes to the pathogenesis of NCLs.