Cell Biology of Annulate Lamellae - an underexplored organelle, Jomon Joseph- National Centre for Cell Science, Pune, India
Annulate lamellae (AL) are subdomains of the endoplasmic reticulum (ER) characterized by stacked membranes containing a subset of nucleoporins including Nup358. The cellular functions of AL are relatively unknown. ER also makes physical connections with mitochondria through ER-mitochondria contact sites (ERMCSs). Recent studies have shown that ERMCS are important in regulating many of the functions mediated by ER and mitochondria such as inter-organelle Ca2+ and lipid transfer, apoptosis, mitochondrial energetics and autophagy. We find that Nup358-positive AL are present at the ERMCSs and depletion of Nup358 results in induction of autophagy. Mechanistically, we show that Nup358 interacts with an ERMCS tethering complex consisting of IP3R, GRP75 and VDAC, which also regulates Ca2+ homeostasis between ER and mitochondria. Depletion of Nup358 reduces the level of mitochondrial porin VDAC, thereby reducing the uptake of Ca2+ from cytosol to mitochondria. As a consequence, Ca2+ released by IP3R from the ER accumulates in the cytosol, which leads to calcium-induced autophagy through activation of the CaMKK2/AMPK pathway. Moreover, we also find a role for Nup358 in regulating the ERMCSs via restricting mTORC2/Akt activation. Our results uncover an unexpected role for AL, and particularly for Nup358, in cellular homeostasis by regulating ERMCSs and their functions.
Host: Antonino Colanzi (
Conference Room, CNR, P. Castellino Campus
