Delhey Leanna M, Nur Kilinc Ekim, Yin Li, Slattery John C, Tippett Marie L, Rose Shannon, Bennuri Sirish C, Kahler Stephen G, Damle Shirish, Legido Agustin, Goldenthal Michael J, Frye Richard E
Arkansas Children's Research Institute, Little Rock, AR 72202, USA.
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
J Clin Med. 2017 Feb 13;6(2):18. doi: 10.3390/jcm6020018.
Treatment for mitochondrial dysfunction is typically guided by expert opinion with a paucity of empirical evidence of the effect of treatment on mitochondrial activity. We examined citrate synthase and Complex I and IV activities using a validated buccal swab method in 127 children with autism spectrum disorder with and without mitochondrial disease, a portion of which were on common mitochondrial supplements. Mixed-model linear regression determined whether specific supplements altered the absolute mitochondrial activity as well as the relationship between the activities of mitochondrial components. Complex I activity was increased by fatty acid and folate supplementation, but folate only effected those with mitochondrial disease. Citrate synthase activity was increased by antioxidant supplementation but only for the mitochondrial disease subgroup. The relationship between Complex I and IV was modulated by folate while the relationship between Complex I and Citrate Synthase was modulated by both folate and B12. This study provides empirical support for common mitochondrial treatments and demonstrates that the relationship between activities of mitochondrial components might be a marker to follow in addition to absolute activities. Measurements of mitochondrial activity that can be practically repeated over time may be very useful to monitor the biochemical effects of treatments.
线粒体功能障碍的治疗通常以专家意见为指导，而关于治疗对线粒体活性影响的实证证据却很少。我们使用经过验证的颊拭子方法，检测了127名患有和未患线粒体疾病的自闭症谱系障碍儿童的柠檬酸合酶以及复合体I和IV的活性，其中一部分儿童正在服用常见的线粒体补充剂。混合模型线性回归确定了特定补充剂是否改变了绝对线粒体活性以及线粒体各组分活性之间的关系。补充脂肪酸和叶酸可提高复合体I的活性，但叶酸仅对患有线粒体疾病的儿童有影响。补充抗氧化剂可提高柠檬酸合酶的活性，但仅对线粒体疾病亚组有效。叶酸调节复合体I和IV之间的关系，而叶酸和维生素B12共同调节复合体I和柠檬酸合酶之间的关系。本研究为常见的线粒体治疗提供了实证支持，并表明除了绝对活性外，线粒体各组分活性之间的关系可能是一个需要追踪的指标。随着时间的推移能够实际重复进行的线粒体活性测量，可能对监测治疗的生化效果非常有用。
