Sunday September 23, 2012 15:15 - 15:45 @ Rhodes 8 

Tuesday September 25, 2012 12:30 - 14:00 @ Rhodes 6 

Keeping the endoplasmic reticulum and mitochondria together

Abstract:

Mitochondria and endoplasmic reticulum (ER) are juxtaposed by specific molecular machinery that we are starting to unravel and that include mitofusin 2 (MFN2), a large mitochondrial GTPase that we identified as the first molecular tether between the two organelles. Today we will discuss the existence of different splice variants of MFN2expressed in human tissues. Splice variants lacking part (Variant 1) or all (Variant 2) of the GTPase domain are localized in ER and Variant 2 is enriched at the interface between ER and mitochondria.  The mitochondrial targeting of full length Mfn2 requires the integrity of coiled-coils 1 and 2, while the transmembrane domain alone is sufficient to target the Mfn2 variants to the ER . Re-expression of ER-specific Mfn2 variants in Mfn2-/- cells rescues ER morphology, corrects ER-mitochondrial tethering and normalizes ER Ca2+ levels, without rescuing mitochondrial morphology. The discovery of ER-specific mitofusin 2 variants reveals the existence of entirely extramitochondrial MFN2 functions responsible for tethering of ER and mitochondria.