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ER-mitochondria contact sites in neurodegeneration: genetic screening approaches to investigate novel disease mechanisms

Published version
Peer-reviewed

Change log

Authors

Wilson, Emma Louise  ORCID logo  https://orcid.org/0000-0002-5600-1622
Metzakopian, Emmanouil  ORCID logo  https://orcid.org/0000-0003-2893-9741

Abstract

Abstract: Mitochondria-ER contact sites (MERCS) are known to underpin many important cellular homoeostatic functions, including mitochondrial quality control, lipid metabolism, calcium homoeostasis, the unfolded protein response and ER stress. These functions are known to be dysregulated in neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD) and amyloid lateral sclerosis (ALS), and the number of disease-related proteins and genes being associated with MERCS is increasing. However, many details regarding MERCS and their role in neurodegenerative diseases remain unknown. In this review, we aim to summarise the current knowledge regarding the structure and function of MERCS, and to update the field on current research in PD, AD and ALS. Furthermore, we will evaluate high-throughput screening techniques, including RNAi vs CRISPR/Cas9, pooled vs arrayed formats and how these could be combined with current techniques to visualise MERCS. We will consider the advantages and disadvantages of each technique and how it can be utilised to uncover novel protein pathways involved in MERCS dysfunction in neurodegenerative diseases.

Description

Funder: Open Targets OTAR050 UK Dementia Research Institute RRZA/175

Keywords

Review Article, /631/80, /631/378/2611, /692/699/375, review-article

Journal Title

Cell Death & Differentiation

Conference Name

Journal ISSN

1350-9047
1476-5403

Volume Title

28

Publisher

Nature Publishing Group UK