RT Journal Article SR Electronic T1 A Role for Presenilins in Autophagy Revisited: Normal Acidification of Lysosomes in Cells Lacking PSEN1 and PSEN2 JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 8633 OP 8648 DO 10.1523/JNEUROSCI.0556-12.2012 VO 32 IS 25 A1 Xulun Zhang A1 Krassimira Garbett A1 Karthikeyan Veeraraghavalu A1 Brian Wilburn A1 Reid Gilmore A1 Karoly Mirnics A1 Sangram S. Sisodia YR 2012 UL http://www.jneurosci.org/content/32/25/8633.abstract AB Presenilins 1 and 2 (PS1 and PS2) are the catalytic subunits of the γ-secretase complex, and genes encoding mutant PS1 and PS2 variants cause familial forms of Alzheimer's disease. Lee et al. (2010) recently reported that loss of PS1 activity lead to impairments in autophagosomal function as a consequence of lysosomal alkalinization, caused by failed maturation of the proton translocating V0a1 subunit of the vacuolar (H+)-ATPase and targeting to the lysosome. We have reexamined these issues in mammalian cells and in brains of mice lacking PS (PScdko) and have been unable to find evidence that the turnover of autophagic substrates, vesicle pH, V0a1 maturation, or lysosome function is altered compared with wild-type counterparts. Collectively, our studies fail to document a role for presenilins in regulating cellular autophagosomal function. On the other hand, our transcriptome studies of PScdko mouse brains reveal, for the first time, a role for PS in regulating lysosomal biogenesis.