Proteinopathies and OXP HOS dysfunction in neurodegenerative diseases.

Kawamata, Hibiki; Manfredi, Giovanni

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 (OXP HOS), 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 OXP HOS.

MITOCHONDRIA; OXIDATIVE phosphorylation; NEURODEGENERATION

Journal of Cell Biology, 2017, Vol 216, Issue 12, p3917

0021-9525

Academic Journal

10.1083/jcb.201709172