In vitro studies in VCP-associated multisystem proteinopathy suggest altered mitochondrial bioenergetics

Mitochondrion
Angèle NalbandianVirginia E Kimonis

Abstract

Mitochondrial dysfunction has recently been implicated as an underlying factor to several common neurodegenerative diseases, including Parkinson's disease, Alzheimer's and amyotrophic lateral sclerosis (ALS). Valosin containing protein (VCP)-associated multisystem proteinopathy is a new hereditary disorder associated with inclusion body myopathy, Paget disease of bone (PDB), frontotemporal dementia (FTD) and ALS. VCP has been implicated in several transduction pathways including autophagy, apoptosis and the PINK1/Parkin cascade of mitophagy. In this report, we characterized VCP patient and mouse fibroblasts/myoblasts to examine their mitochondrial dynamics and bioenergetics. Using the Seahorse XF-24 technology, we discovered decreased spare respiratory capacity (measurement of extra ATP that can be produced by oxidative phosphorylation in stressful conditions) and increased ECAR levels (measurement of glycolysis), and proton leak in VCP human fibroblasts compared with age- and sex-matched unaffected first degree relatives. We found decreased levels of ATP and membrane potential, but higher mitochondrial enzyme complexes II+III and complex IV activities in the patient VCP myoblasts when compared to the values of the control cell...Continue Reading

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Citations

Feb 3, 2016·Molecular and Cellular Neurosciences·Maria Sara Cipolat MisStefania Corti
Nov 18, 2015·Muscle & Nerve·Mohamed KazamelMargherita Milone
Feb 9, 2018·Disease Models & Mechanisms·Orietta PansarasaCristina Cereda
Dec 11, 2019·Genes·Christine GermeysLudo Van Den Bosch
Jan 14, 2021·Biochemical Society Transactions·Hongyang ShuDao Wen Wang
Jan 14, 2021·Brain : a Journal of Neurology·Matilde SassaniThomas M Jenkins
Aug 2, 2020·Mitochondrion·Rebecca BornsteinSimon C Johnson

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