Key result
Mutations in ER-phagy receptors such as FAM134B and ARL6IP1 impair the degradation of ER fragments and misfolded proteins, leading to ER stress and subsequent sensory and autonomic neurodegeneration.
Dysfunction in ER-phagy receptors disrupts ER homeostasis and is a key mechanism underlying certain neurodegenerative disorders.
May guide genetic evaluation in unexplained neurodegeneration; leaves open whether modulating ER-phagy alters progression.
Autophagy is a process to target substrates for lysosomal degradation, which starts with the enclosure of the substrate by the LC3-labelled isolation membrane and the subsequent fusion with lysosomes. Selectivity of this process can be achieved via autophagy receptors. In recent years, several receptors which target ER subdomains for degradation via autophagy (reticulophagy or ER-phagy) have been described. Some of which are associated with neurodegenerative disorders.
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Hübner et al. (2024) conducted a review in Neurodegenerative disorders. ER-phagy receptor mutations (FAM134B, ARL6IP1) was evaluated. Mutations in ER-phagy receptors such as FAM134B and ARL6IP1 impair the degradation of ER fragments and misfolded proteins, leading to ER stress and subsequent sensory and autonomic neurodegeneration.
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