Presenilin 2 Modulates Endoplasmic Reticulum-Mitochondria Coupling by Tuning the Antagonistic Effect of Mitofusin 2.

Abstract:

:Communication between organelles plays key roles in cell biology. In particular, physical and functional coupling of the endoplasmic reticulum (ER) and mitochondria is crucial for regulation of various physiological and pathophysiological processes. Here, we demonstrate that Presenilin 2 (PS2), mutations in which underlie familial Alzheimer's disease (FAD), promotes ER-mitochondria coupling only in the presence of mitofusin 2 (Mfn2). PS2 is not necessary for the antagonistic effect of Mfn2 on organelle coupling, although its abundance can tune it. The two proteins physically interact, whereas their homologues Mfn1 and PS1 are dispensable for this interplay. Moreover, PS2 mutants associated with FAD are more effective than the wild-type form in modulating ER-mitochondria tethering because their binding to Mfn2 in mitochondria-associated membranes is favored. We propose a revised model for ER-mitochondria interaction to account for these findings and discuss possible implications for FAD pathogenesis.

journal_name

Cell Rep

journal_title

Cell reports

authors

Filadi R,Greotti E,Turacchio G,Luini A,Pozzan T,Pizzo P

doi

10.1016/j.celrep.2016.05.013

subject

Has Abstract

pub_date

2016-06-07 00:00:00

pages

2226-2238

issue

10

issn

2211-1247

pii

S2211-1247(16)30580-0

journal_volume

15

pub_type

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