In-depth proteomic analysis of mammalian mitochondria-associated membranes (MAM)

Abstract

The endoplasmic reticulum (ER) and mitochondria communicate via contact sites known as mitochondria-associated ER membranes or MAM. The region has emerged as the primary area of Ca(2+) traffic between the two organelles, and as such, has been implicated in the regulation of protein folding, oxidative phosphorylation, and Ca(2+)-mediated apoptosis. In order to better understand biological processes and molecular functions at the MAM, we report a global mass spectrometry-based proteomic evaluation of the MAM obtained from mouse brain samples. Gel-assisted sample preparation in conjunction with our two-dimensional chromatography approach allowed for the identification of 1,212 high confidence proteins. Bioinformatic interrogation of this protein catalogue using Ingenuity Pathway Analysis revealed new potential connections between our list of MAM proteins and neurodegenerative diseases in addition to anticipated biological processes. Based on our results, we postulate that proteins of the MAM may play essential roles in dysfunctions responsible for several neurological disorders in addition to facilitating key cellular survival processes.