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首页> 外文期刊>Molecular and Cellular Biology >Role of ALDP (ABCD1) and Mitochondria in X-Linked Adrenoleukodystrophy
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Role of ALDP (ABCD1) and Mitochondria in X-Linked Adrenoleukodystrophy

机译：ALDP（ABCD1）和线粒体在X联肾上腺皮质营养不良中的作用

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Peroxisomal disorders have been associated with malfunction of peroxisomal metabolic pathways, but the pathogenesis of these disorders is largely unknown. X-linked adrenoleukodystrophy (X-ALD) is associated with elevated levels of very-long-chain fatty acids (VLCFA; C) that have been attributed to reduced peroxisomal VLCFA β-oxidation activity. Previously, our laboratory and others have reported elevated VLCFA levels and reduced peroxisomal VLCFA β-oxidation in human and mouse X-ALD fibroblasts. In this study, we found normal levels of peroxisomal VLCFA β-oxidation in tissues from ALD mice with elevated VLCFA levels. Treatment of ALD mice with pharmacological agents resulted in decreased VLCFA levels without a change in VLCFA β-oxidation activity. These data indicate that ALDP does not determine the rate of VLCFA β-oxidation and that VLCFA levels are not determined by the rate of VLCFA β-oxidation. The rate of peroxisomal VLCFA β-oxidation in human and mouse fibroblasts in vitro is affected by the rate of mitochondrial long-chain fatty acid β-oxidation. We hypothesize that ALDP facilitates the interaction between peroxisomes and mitochondria, resulting, when ALDP is deficient in X-ALD, in increased VLCFA accumulation despite normal peroxisomal VLCFA β-oxidation in ALD mouse tissues. In support of this hypothesis, mitochondrial structural abnormalities were observed in adrenal cortical cells of ALD mice.
机译：过氧化物酶体紊乱已与过氧化物酶体代谢途径的功能障碍有关，但这些疾病的发病机理在很大程度上尚不清楚。 X联肾上腺白质营养不良症（X-ALD）与超长链脂肪酸（VLCFA; C ）的升高水平有关，这归因于过氧化物酶体VLCFAβ氧化活性的降低。以前，我们的实验室和其他实验室已经报道了人和小鼠X-ALD成纤维细胞中VLCFA含量升高和过氧化物酶体VLCFAβ氧化降低。在这项研究中，我们发现VLCFA水平升高的ALD小鼠组织中过氧化物酶体VLCFAβ-氧化的正常水平。用药物治疗ALD小鼠导致VLCFA水平降低，而VLCFAβ-氧化活性不变。这些数据表明，ALDP不能确定VLCFAβ-氧化率，VLCFA水平也不能由VLCFAβ-氧化率来确定。体外人类和小鼠成纤维细胞中的过氧化物酶体VLCFAβ氧化速率受线粒体长链脂肪酸β氧化速率的影响。我们假设ALDP促进过氧化物酶体与线粒体之间的相互作用，导致ALDP缺乏X-ALD时，尽管ALD小鼠组织中过氧化物酶体的VLCFAβ氧化正常，但VLCFA积累增加。支持该假设的是，在ALD小鼠的肾上腺皮质细胞中观察到线粒体结构异常。

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