Mitochondria-ER Tethering in Neurodegenerative Diseases
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REVIEW PAPER
Mitochondria‑ER Tethering in Neurodegenerative Diseases Reza Raeisossadati1 · Merari F. R. Ferrari1 Received: 22 August 2020 / Accepted: 11 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Organelles juxtaposition has been detected for decades, although only recently gained importance due to a pivotal role in the regulation of cellular processes dependent on membrane contact sites. Endoplasmic reticulum (ER) and mitochondria interaction is a prime example of organelles contact sites. Mitochondria-associated membranes (MAM) are proposed to harbor ER-mitochondria tether complexes, mainly when these organelles are less than 30 nm apart. Dysfunctions of proteins located at the MAM are associated with neurodegenerative diseases such as Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis, as well as neurodevelopmental disorders; hence any malfunction in MAM can potentially trigger cell death. This review will focus on the role of ER-mitochondria contact sites, regarding calcium homeostasis, lipid metabolism, autophagy, morphology and dynamics of mitochondria, mainly in the context of neurodegenerative diseases. Approaches that have been employed so far to study organelles contact sites, as well as methods that were not used in neurosciences yet, but are promising and accurate ways to unveil the functions of MAM during neurodegeneration, is also discussed in the present review. Keyword Mitochondria-associated membranes (MAM) · Contact sites methodologies · Autophagy · Lipid metabolism · Calcium · Neurodegeneration Abbreviations α-syn Alpha-synuclein Aβ Amyloid-beta peptide ACAT1 Cholesterol acyltransferase/sterol O-acyltransferase 1 (same as SOAT1) AD Alzheimer’s disease ALS Amyotrophic lateral sclerosis APEX Ascorbate peroxidase APOE4 Apolipoprotein E4 APP Amyloid precursor protein ATG2A Autophagy-related protein 2 homolog A ATG9A Autophagy-related protein 9 homolog A ATG14L Autophagy-related 14-like BAP31 B-cell receptor-associated protein 31 BECN1 Beclin-1 * Reza Raeisossadati [email protected] * Merari F. R. Ferrari [email protected] 1
Departamento de Genetica e Biologia Evolutiva, Instituto de Biociencias, Universidade de Sao Paulo, Sao Paulo, SP, Brazil
BiC Bimolecular complementation BioID Proximity based biotin identification BRET Bioluminescence resonance energy transfer CACNA1A Calcium Voltage-Gated Channel Subunit Alpha1 A CE Cholesteryl-ester CLEM Correlative light and electron microscopy CMT2A Charcot–Marie–Tooth type 2A Cryo-ET Electron cryo-tomography Cryo-FIB Cryo-focused ion beam ddFP Dimerization-dependent fluorescent protein DFCP1 Double FYVE domain-containing protein 1 DGAT2 Diacylglycerol O-acyltransferase 2 DRP1 Dynamin-Related Protein 1 EI24 Etoposide-induced protein 2.4 EM Electron microscopy ER Endoplasmic reticulum FACL4 Fatty acid CoA ligase 4 (same as ACS4) FIB-SEM Focused ion beam-scanning EM
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FIP200 Focal adhesion kinase (FAK) family interacting protein of 200
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