Mitochondrial fatty acids and neurodegenerative disorders
|Author:||Kastaniotis, Alexander J.1; Autio, Kaija J.1; Nair, Remya R.2|
1Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
2Mammalian Genetics Unit, MRC Harwell Institute, Oxfordshire, UK
|Online Access:||PDF Full Text (PDF, 1.2 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe202103086736
|Publish Date:|| 2021-03-08
Fatty acids in mitochondria, in sensu stricto, arise either as β-oxidation substrates imported via the carnitine shuttle or through de novo synthesis by the mitochondrial fatty acid synthesis (mtFAS) pathway. Defects in mtFAS or processes involved in the generation of the mtFAS product derivative lipoic acid (LA), including iron-sulfur cluster synthesis required for functional LA synthase, have emerged only recently as etiology for neurodegenerative disease. Intriguingly, mtFAS deficiencies very specifically affect CNS function, while LA synthesis and attachment defects have a pleiotropic presentation beyond neurodegeneration. Typical mtFAS defect presentations include optical atrophy, as well as basal ganglia defects associated with dystonia. The phenotype display of patients with mtFAS defects can resemble the presentation of disorders associated with coenzyme A (CoA) synthesis. A recent publication links these processes together based on the requirement of CoA for acyl carrier protein maturation. MtFAS defects, CoA synthesis- as well as Fe-S cluster-deficiencies share lack of LA as a common symptom.
|Type of Publication:||
A2 Review article in a scientific journal
|Field of Science:||
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Academy of Finland (Grant Number 314925) and the Sigrid Juselius Foundation.
|Academy of Finland Grant Number:||
314925 (Academy of Finland Funding decision)
© The Author(s) 2020. Reprinted by permission of SAGE Publications. The final authenticated version is available online at https://doi.org/10.1177/1073858420936162.