Loss of proteins associated with amyotrophic lateral sclerosis affects lysosomal acidification via different routes

Autophagy. 2019 Aug;15(8):1467-1469. doi: 10.1080/15548627.2019.1609863. Epub 2019 Apr 28.


Abnormal accumulation of proteins is a hallmark of a variety of neurological diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Maintenance of protein homeostasis (proteostasis) in neurons via proteasomal and macroautophagy/autophagy-lysosomal degradation is thought to be central for proper neuronal function and survival. We recently reported evolutionarily conserved roles for two ALS-linked proteins, UBQLN2 (ubiquilin 2) and VAPB, in regulation of lysosomal degradation. Ubiquilins are required for v-ATPase-mediated lysosomal acidification, whereas VAPs are required for the PtdIns4P-mediated endo-lysosomal trafficking pathway.

Keywords: ALS; Drosophila; ER stress; MTOR; lysosomal acidification; v-ATPase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acids / metabolism*
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Humans
  • Lysosomes / metabolism*
  • Models, Biological
  • Proteins / metabolism*
  • Ubiquitins / metabolism
  • Vesicular Transport Proteins / metabolism


  • Acids
  • Proteins
  • Ubiquitins
  • Vesicular Transport Proteins