TY - JOUR
T1 - Elevated p62/SQS TM1 determines the fate of autophagy-deficient neural stem cells by increasing superoxide
AU - Wang, Chenran
AU - Chen, Song
AU - Yeo, Syn
AU - Karsli-Uzunbas, Gizem
AU - White, Eileen
AU - Mizushima, Noboru
AU - Virgin, Herbert W.
AU - Guan, Jun Lin
N1 - Publisher Copyright:
© 2016 Wang et al.
PY - 2016
Y1 - 2016
N2 - Autophagy plays important roles in many biological processes, but our understanding of the mechanisms regulating stem cells by autophagy is limited. Interpretations of earlier studies of autophagy using knockouts of single genes are confounded by accumulating evidence for other functions of many autophagy genes. Here, we show that, in contrast to Fip200 deletion, inhibition of autophagy by deletion of Atg5, Atg16L1, or Atg7 does not impair the maintenance and differentiation of postnatal neural stem cells (NSCs). Only Fip200 deletion, but not Atg5, Atg16L1, or Atg7 deletion, caused p62/sequestome1 aggregates to accumulate in NSCs. Fip200 and p62 double conditional knockout mice demonstrated that p62 aggregate formation triggers aberrant superoxide increases by impairing superoxide dismutase functions. By comparing the inhibition of autophagy by deletion of Atg5, Atg16L1, or Atg7 with Fip200 deletion, we revealed a critical role of increased p62 in determining the fate of autophagy-deficient NSCs through intracellular superoxide control.
AB - Autophagy plays important roles in many biological processes, but our understanding of the mechanisms regulating stem cells by autophagy is limited. Interpretations of earlier studies of autophagy using knockouts of single genes are confounded by accumulating evidence for other functions of many autophagy genes. Here, we show that, in contrast to Fip200 deletion, inhibition of autophagy by deletion of Atg5, Atg16L1, or Atg7 does not impair the maintenance and differentiation of postnatal neural stem cells (NSCs). Only Fip200 deletion, but not Atg5, Atg16L1, or Atg7 deletion, caused p62/sequestome1 aggregates to accumulate in NSCs. Fip200 and p62 double conditional knockout mice demonstrated that p62 aggregate formation triggers aberrant superoxide increases by impairing superoxide dismutase functions. By comparing the inhibition of autophagy by deletion of Atg5, Atg16L1, or Atg7 with Fip200 deletion, we revealed a critical role of increased p62 in determining the fate of autophagy-deficient NSCs through intracellular superoxide control.
UR - http://www.scopus.com/inward/record.url?scp=84960389624&partnerID=8YFLogxK
U2 - 10.1083/jcb.201507023
DO - 10.1083/jcb.201507023
M3 - Article
C2 - 26929451
AN - SCOPUS:84960389624
SN - 0021-9525
VL - 212
SP - 545
EP - 560
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -