Janssen Antoon J M, Schuelke Markus, Smeitink Jan A M, Trijbels Frans J M, Sengers Rob C A, Lucke Barbara, Wintjes Liesbeth T M, Morava Eva, van Engelen Baziel G M, Smits Bart W, Hol Frans A, Siers Marloes H, Ter Laak Henk, van der Knaap Marjo S, Van Spronsen Francjan J, Rodenburg Richard J T, van den Heuvel Lambert P
Department of Pediatrics and Laboratory of Pediatrics and Neurology, Nijmegen Centre for Mitochondrial Disorders, Radboud University Medical Centre, Nijmegen, The Netherlands.
Ann Neurol. 2008 Apr;63(4):473-81. doi: 10.1002/ana.21328.
The mitochondrial energy-generating system (MEGS) encompasses the mitochondrial enzymatic reactions from oxidation of pyruvate to the export of adenosine triphosphate. It is investigated in intact muscle mitochondria by measuring the pyruvate oxidation and adenosine triphosphate production rates, which we refer to as the "MEGS capacity." Currently, little is known about MEGS pathology in patients with mutations in the mitochondrial DNA. Because MEGS capacity is an indicator for the overall mitochondrial function related to energy production, we searched for a correlation between MEGS capacity and 3243A-->G mutation load in muscle of patients with the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) syndrome.
In muscle tissue of 24 patients with the 3243A-->G mutation, we investigated the MEGS capacity, the respiratory chain enzymatic activities, and the 3243A-->G mutation load. To exclude coinciding mutations, we sequenced all 22 mitochondrial transfer RNA genes in the patients, if possible.
We found highly significant differences between patients and control subjects with respect to the MEGS capacity and complex I, III, and IV activities. MEGS-related measurements correlated considerably better with the mutation load than respiratory chain enzyme activities. We found no additional mutations in the mitochondrial transfer RNA genes of the patients.
The results show that MEGS capacity has a greater sensitivity than respiratory chain enzymatic activities for detection of subtle mitochondrial dysfunction. This is important in the workup of patients with rare or new mitochondrial DNA mutations, and with low mutation loads. In these cases we suggest to determine the MEGS capacity.
线粒体能量生成系统（MEGS）包括从丙酮酸氧化到三磷酸腺苷输出的线粒体酶促反应。通过测量丙酮酸氧化和三磷酸腺苷生成速率来研究完整肌肉线粒体中的该系统，我们将其称为“MEGS能力”。目前，对于线粒体DNA发生突变的患者的MEGS病理学知之甚少。由于MEGS能力是与能量产生相关的整体线粒体功能的指标，我们探寻了患有线粒体脑肌病伴乳酸血症和卒中样发作（MELAS）综合征患者肌肉中MEGS能力与3243A→G突变负荷之间的相关性。
在24例携带3243A→G突变的患者的肌肉组织中，我们研究了MEGS能力、呼吸链酶活性以及3243A→G突变负荷。为排除同时存在的突变，我们尽可能对患者所有22个线粒体转移RNA基因进行了测序。
我们发现患者与对照受试者在MEGS能力以及复合体I、III和IV活性方面存在高度显著差异。与呼吸链酶活性相比，与MEGS相关的测量值与突变负荷的相关性要高得多。我们在患者的线粒体转移RNA基因中未发现其他突变。
结果表明，对于检测细微的线粒体功能障碍，MEGS能力比呼吸链酶活性具有更高的敏感性。这对于罕见或新的线粒体DNA突变且突变负荷较低的患者的检查很重要。在这些情况下，我们建议测定MEGS能力。
