Mitochondria-ER Tethering in Neurodegenerative Diseases

Author(s)

Raeisossadati, Reza ; Ferrari, Merari F. R.

• Document type: Journal article
• Source: Cellular and Molecular Neurobiology; v. 42, n. 4, p. 14-pg., 2020-11-16.

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. (AU)

• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/07592-4 - The role of quality control mechanisms in the loss of proteostasis in age-dependent neurodegenerative diseases
• Grantee: Merari de Fátima Ramires Ferrari
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/01290-9 - Analysis of ER and mitochondria dynamics and interaction during protein aggregation
• Grantee: Seyed Reza Raeisossadati
• Support Opportunities: Scholarships in Brazil - Post-Doctoral