PT  - JOURNAL ARTICLE
AU  - Xulun Zhang
AU  - Krassimira Garbett
AU  - Karthikeyan Veeraraghavalu
AU  - Brian Wilburn
AU  - Reid Gilmore
AU  - Karoly Mirnics
AU  - Sangram S. Sisodia
TI  - A Role for Presenilins in Autophagy Revisited: Normal Acidification of Lysosomes in Cells Lacking <em>PSEN1</em> and <em>PSEN2</em>
AID  - 10.1523/JNEUROSCI.0556-12.2012
DP  - 2012 Jun 20
TA  - The Journal of Neuroscience
PG  - 8633--8648
VI  - 32
IP  - 25
4099  - http://www.jneurosci.org/content/32/25/8633.short
4100  - http://www.jneurosci.org/content/32/25/8633.full
SO  - J. Neurosci.2012 Jun 20; 32
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.