Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
Mammalian Genetics Unit, MRC Harwell Institute, Oxfordshire, UK.
Neuroscientist. 2021 Apr;27(2):143-158. doi: 10.1177/1073858420936162. Epub 2020 Jul 9.
Fatty acids in mitochondria, in , arise either as β-oxidation substrates imported the carnitine shuttle or through 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.
线粒体中的脂肪酸，要么作为肉碱穿梭系统的β-氧化底物被导入，要么通过线粒体脂肪酸合成（mtFAS）途径合成。mtFAS 或生成 mtFAS 产物衍生物硫辛酸（LA）的相关过程中的缺陷，包括 LA 合酶所需的铁硫簇合成，最近才被确定为神经退行性疾病的病因。有趣的是，mtFAS 缺乏症非常特异性地影响中枢神经系统功能，而 LA 合成和连接缺陷在神经退行性病变之外具有多效性表现。典型的 mtFAS 缺陷表现包括视神经萎缩，以及与肌张力障碍相关的基底节缺陷。mtFAS 缺陷患者的表型表现类似于与辅酶 A（CoA）合成相关的疾病的表现。最近的一篇出版物基于酰基辅酶 A 成熟所需的 CoA，将这些过程联系在一起。mtFAS 缺陷、CoA 合成以及 Fe-S 簇缺陷均缺乏 LA 作为共同症状。
