Connection lost, mam: Errors in er–mitochondria connections in neurodegenerative diseases

Abstract

Mitochondria associated membranes (MAMs), as the name suggests, are the membranes that physically and biochemically connect mitochondria with endoplasmic reticulum. MAMs not only structurally but also functionally connect these two important organelles within the cell which were previously thought to exist independently. There are multiple points of communication between ER–mitochondria and MAMs play an important role in both ER and mitochondria functions such as Ca2+ homeostasis, proteostasis, mitochondrial bioenergetics, movement, and mitophagy. The number of disease-related proteins and genes being associated with MAMs has been continually on the rise since its discovery. There is an overwhelming overlap between the biochemical functions of MAMs and processes affected in neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Thus, MAMs have received well-deserving and much delayed attention as modulators for ER–mitochondria communication and function. This review briefly discusses the recent progress made in this now fast developing field full of promise for very exciting future therapeutic discoveries.