Deficiencies of medium-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein, isolated long-chain 3-hydroxyacyl-CoA dehydrogenase, and very long-chain acyl-CoA dehydrogenase activities are considered the most frequent fatty acid oxidation defects (FAOD). They are biochemically characterized by the accumulation of medium-chain, long-chain hydroxyl, and long-chain fatty acids and derivatives, respectively, in tissues and biological fluids of the affected patients. Clinical manifestations commonly include hypoglycemia, cardiomyopathy, and recurrent rhabdomyolysis. Although the pathogenesis of these diseases is still poorly understood, energy deprivation secondary to blockage of fatty acid degradation seems to play an important role. However, recent evidence indicates that the predominant fatty acids accumulating in these disorders disrupt mitochondrial functions and are involved in their pathophysiology, possibly explaining the lactic acidosis, mitochondrial morphological alterations, and altered mitochondrial biochemical parameters found in tissues and cultured fibroblasts from some affected patients and also in animal models of these diseases. In this review, we will update the present knowledge on disturbances of mitochondrial bioenergetics, calcium homeostasis, uncoupling of oxidative phosphorylation, and mitochondrial permeability transition induction provoked by the major fatty acids accumulating in prevalent FAOD. It is emphasized that further in vivo studies carried out in tissues from affected patients and from animal genetic models of these disorders are necessary to confirm the present evidence mostly achieved from in vitro experiments.

中链酰基辅酶A脱氢酶、线粒体三功能蛋白、分离的长链3-羟酰基辅酶A脱氢酶和极长链酰基辅酶A脱氢酶活性的缺陷被认为是最常见的脂肪酸氧化缺陷(FAOD)。它们的生化特征是在受影响患者的组织和生物体液中分别积累中链、长链羟基和长链脂肪酸及其衍生物。临床表现通常包括低血糖、心肌病和复发性横纹肌溶解症。尽管这些疾病的发病机制仍知之甚少，但脂肪酸降解受阻继发的能量剥夺似乎发挥着重要作用。然而，最近的证据表明，这些疾病中积累的主要脂肪酸会破坏线粒体功能并参与其病理生理学，这可能解释了在一些受影响患者的组织和培养的成纤维细胞中发现的乳酸性酸中毒、线粒体形态改变和线粒体生化参数改变。也在这些疾病的动物模型中。在这篇综述中，我们将更新目前关于线粒体生物能量学、钙稳态、氧化磷酸化解偶联以及常见FAOD中主要脂肪酸积累引起的线粒体通透性转变诱导的紊乱的知识。需要强调的是，进一步体内有必要在受影响患者的组织和这些疾病的动物遗传模型中进行研究，以证实目前的证据主要来自体外实验。