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Mitochondria and endoplasmic reticulum crosstalk in amyotrophic lateral sclerosis.

TitleMitochondria and endoplasmic reticulum crosstalk in amyotrophic lateral sclerosis.
Publication TypeJournal Article
Year of Publication2016
AuthorsManfredi G, Kawamata H
JournalNeurobiol Dis
Volume90
Pagination35-42
Date Published2016 Jun
ISSN1095-953X
KeywordsAmyotrophic Lateral Sclerosis, Animals, Endoplasmic Reticulum, Humans, Mitochondria
Abstract

Physical and functional interactions between mitochondria and the endoplasmic reticulum (ER) are crucial for cell life. These two organelles are intimately connected and collaborate to essential processes, such as calcium homeostasis and phospholipid biosynthesis. The connections between mitochondria and endoplasmic reticulum occur through structures named mitochondria associated membranes (MAMs), which contain lipid rafts and a large number of proteins, many of which serve multiple functions at different cellular sites. Growing evidence strongly suggests that alterations of ER-mitochondria interactions are involved in neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), a devastating and rapidly fatal motor neuron disease. Mutations in proteins that participate in ER-mitochondria interactions and MAM functions are increasingly being associated with genetic forms of ALS and other neurodegenerative diseases. This evidence strongly suggests that, rather than considering the two organelles separately, a better understanding of the disease process can derive from studying the alterations in their crosstalk. In this review we discuss normal and pathological ER-mitochondria interactions and the evidence that link them to ALS.

DOI10.1016/j.nbd.2015.08.004
Alternate JournalNeurobiol. Dis.
PubMed ID26282323
PubMed Central IDPMC4754163
Grant List2R01NS051419-05 / NS / NINDS NIH HHS / United States
R01 NS093872 / NS / NINDS NIH HHS / United States
R01 NS051419 / NS / NINDS NIH HHS / United States
R01 NS084486 / NS / NINDS NIH HHS / United States
1R01NS062055-01 / NS / NINDS NIH HHS / United States
R01 NS062055 / NS / NINDS NIH HHS / United States