Skip to main content
. Author manuscript; available in PMC: 2014 Dec 1.
Published in final edited form as: Biochim Biophys Acta. 2013 Jul 10;1833(12):10.1016/j.bbamcr.2013.06.028. doi: 10.1016/j.bbamcr.2013.06.028

Figure 2. Dual function of BI-1 in ER stress and autophagy.

Figure 2

BI-1 modulates ER stress and autophagy by independent mechanisms. BI-1 suppresses IRE1α by forming a complex with IRE1α, which then nullifies both its endoribonuclease (XBP-1) and kinase activity (JNK). Via an IP3R-dependent mechanism, BI-1 also reduces the steady-state levels of ER Ca2+, which causes a corresponding decline in mitochondrial Ca2+ levels and reduces mitochondria bioenergetics. Reduction in ATP levels (rise in AMP) activates the intracellular energy sensor AMPK, which activates autophagy via effects on Atg1 (Ulk1/Ulk2). BI-1 has also been shown to associate with Bcl-2 to regulate Ca2+ homeostasis, which could also indirectly influence autophagy.