Year: 2019
Type: review
Abstract: Mitochondrial respiratory deficiencies have been observed in numerous neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. For decades, these reductions in oxidative phosphorylation (OxPhos) have been presumed to trigger an overall bioenergetic crisis in the neuron, resulting in cell death. While the connection between respiratory defects and neuronal death has never been proven, this hypothesis has been supported by the detection of nonspecific mitochondrial DNA mutations in these disorders. These findings led to the notion that mitochondrial respiratory defects could be initiators of these common neurodegenerative disorders, instead of being consequences of a prior insult, a theory we believe to be misconstrued. Herein, we review the roots of this mitochondrial hypothesis and offer a new perspective wherein mitochondria are analyzed not only from the OxPhos point of view, but also as a complex organelle residing at the epicenter of many metabolic pathways.
DOI: 10.1172/jci120848
Institution: Columbia University Irving Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funders: U.S. Department of Defense, Michael J. Fox Foundation for Parkinson's Research, Leir Foundation, National Institutes of Health, National Institute on Aging, National Institute of Neurological Disorders and Stroke, National Institute of Biomedical Imaging and Bioengineering, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Endoplasmic Reticulum Mitochondrial membranes in Alzheimer's disease, Optimization of ultrasound-facilitated blood-brain barrier opening, Role of C99 in the regulation of lipid metabolism- Relevance to Alzheimer's disease, Mitochondrial Encephalomyopathies and Mental Retardation, Non-cell Autonomous Role of Synuclein in Neurodegeneration, Mechanisms of Axon Pathology in ALS
OpenAlex ID: W2908362631