Brinkmann Christian, Przyklenk Axel, Metten Alexander, Schiffer Thorsten, Bloch Wilhelm, Brixius Klara, Gehlert Sebastian
a Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine , German Sport University Cologne , Germany.
b IST University of Applied Sciences , Düsseldorf , Germany.
Endocr Res. 2017 Nov;42(4):325-330. doi: 10.1080/07435800.2017.1323914. Epub 2017 May 24.
Mitophagy is a form of autophagy for the elimination of mitochondria. Mitochondrial content and function are reduced in the skeletal muscle of patients with type 2 diabetes mellitus (T2DM). Physical training has been shown to restore mitochondrial capacity in T2DM patients, but the role of mitophagy has not been examined in this context. This study analyzes the impact of a 3-month endurance training on important skeletal muscle mitophagy regulatory proteins and oxidative phosphorylation (OXPHOS) complexes in T2DM patients.
Muscle biopsies were obtained from eight overweight/obese T2DM men (61±10 years) at T1 (6 weeks pre-training), T2 (1 week pre-training), and T3 (3 to 4 days post-training). Protein contents were determined by Western blotting.
The training increased mitochondrial complex II significantly (T2-T3: +29%, p = 0.037). The protein contents of mitophagy regulatory proteins (phosphorylated form of forkhead box O3A (pFOXO3A), mitochondrial E3 ubiquitin protein ligase-1 (MUL1), Bcl-2/adenovirus E1B 19-kD interacting protein-3 (BNIP3), microtubule-associated protein 1 light chain-3B (the ratio LC3B-II/LC3B-I was determined)) did not differ significantly between T1, T2, and T3.
The results imply that training-induced changes in OXPHOS subunits (significant increase in complex II) are not accompanied by changes in mitophagy regulatory proteins in T2DM men. Future studies should elucidate whether acute exercise might affect mitophagic processes in T2DM patients (and whether a transient regulation of mitophagy regulatory proteins is evident) to fully clarify the role of physical activity and mitophagy for mitochondrial health in this particular patient group.
线粒体自噬是一种清除线粒体的自噬形式。2型糖尿病（T2DM）患者的骨骼肌中线粒体含量和功能降低。体育锻炼已被证明可恢复T2DM患者的线粒体功能，但在此背景下尚未研究线粒体自噬的作用。本研究分析了为期3个月的耐力训练对T2DM患者重要的骨骼肌线粒体自噬调节蛋白和氧化磷酸化（OXPHOS）复合物的影响。
从8名超重/肥胖的T2DM男性（61±10岁）身上获取肌肉活检样本，分别在训练前6周（T1）、训练前1周（T2）和训练后3至4天（T3）进行。通过蛋白质印迹法测定蛋白质含量。
训练使线粒体复合物II显著增加（T2 - T3：增加29%，p = 0.037）。线粒体自噬调节蛋白（叉头框O3A磷酸化形式（pFOXO3A）、线粒体E3泛素蛋白连接酶-1（MUL1）、Bcl-2/腺病毒E1B 19-kD相互作用蛋白-3（BNIP3）、微管相关蛋白1轻链-3B（测定LC3B-II/LC3B-I比值））的蛋白质含量在T1、T2和T3之间无显著差异。
结果表明，训练引起的OXPHOS亚基变化（复合物II显著增加）在T2DM男性中并未伴随线粒体自噬调节蛋白的变化。未来的研究应阐明急性运动是否可能影响T2DM患者的线粒体自噬过程（以及线粒体自噬调节蛋白的短暂调节是否明显），以充分阐明体育活动和线粒体自噬对该特定患者群体线粒体健康的作用。
