Proteinopathies and OXPHOS dysfunction in neurodegenerative diseases.

TitleProteinopathies and OXPHOS dysfunction in neurodegenerative diseases.
Publication TypeJournal Article
Year of Publication2017
AuthorsKawamata H, Manfredi G
JournalJ Cell Biol
Date Published2017 Dec 04
Keywordsalpha-Synuclein, Amyloid beta-Peptides, Animals, Gene Expression Regulation, Humans, Mitochondria, Mitochondrial Proteins, Neurodegenerative Diseases, Oxidative Phosphorylation, Protein Interaction Mapping, Proteostasis Deficiencies

Mitochondria participate in essential processes in the nervous system such as energy and intermediate metabolism, calcium homeostasis, and apoptosis. Major neurodegenerative diseases are characterized pathologically by accumulation of misfolded proteins as a result of gene mutations or abnormal protein homeostasis. Misfolded proteins associate with mitochondria, forming oligomeric and fibrillary aggregates. As mitochondrial dysfunction, particularly of the oxidative phosphorylation system (OXPHOS), occurs in neurodegeneration, it is postulated that such defects are caused by the accumulation of misfolded proteins. However, this hypothesis and the pathological role of proteinopathies in mitochondria remain elusive. In this study, we critically review the proposed mechanisms whereby exemplary misfolded proteins associate with mitochondria and their consequences on OXPHOS.

Alternate JournalJ. Cell Biol.
PubMed ID29167179
PubMed Central IDPMC5716291
Grant ListR01 NS062055 / NS / NINDS NIH HHS / United States
R01 NS093872 / NS / NINDS NIH HHS / United States