Mitochondrial Redox Status Regulates Glycogen Metabolism via Glycogen Phosphorylase Activity.

IF 6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ikko Sakamoto, Shuichi Shibuya, Hidetoshi Nojiri, Kotaro Takeno, Hiroshi Nishimune, Keisuke Yaku, Takashi Nakagawa, Muneaki Ishijima, Takahiko Shimizu
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Abstract

Mitochondria and glycogen are co-distributed in skeletal muscles to regulate the metabolic status. Mitochondria are also redox centers that regulate the muscle function during exercise. However, the pathophysiological relationship between the mitochondrial redox status and glycogen metabolism in the muscle remains unclear. In the present study, we examined the pathological effects of mitochondrial dysfunction induced by mitochondrial superoxide dismutase (SOD2) depletion on glycogen metabolism. We found that muscle glycogen was significantly accumulated in association with motor dysfunction in mice with a muscle-specific SOD2 deficiency. Muscle glycogen phosphorylase (GP-M) activity, which is a key enzyme for glycogen degradation at times when energy is needed (e.g., during exercise), was significantly decreased in the mutant muscle. Moreover, the GP-M activity on normal muscle sections decreased after treatment with paraquat, a superoxide generator. In contrast, treatment with antioxidants reversed the GP-M activity and motor disturbance of the mutant mice, indicating that GP-M activity was reversibly regulated by the redox balance. These results demonstrate that the maintenance of the mitochondrial redox balance regulates glycogen metabolism via GP-M activity.

线粒体氧化还原状态通过糖原磷酸化酶活性调节糖原代谢
线粒体和糖原共同分布在骨骼肌中,调节新陈代谢状态。线粒体也是氧化还原中心,在运动过程中调节肌肉功能。然而,线粒体氧化还原状态与肌肉中糖原代谢之间的病理生理关系仍不清楚。在本研究中,我们研究了线粒体超氧化物歧化酶(SOD2)耗竭诱导的线粒体功能障碍对糖原代谢的病理影响。我们发现,在肌肉特异性 SOD2 缺乏的小鼠中,肌糖原明显累积,同时伴有运动功能障碍。肌肉糖原磷酸化酶(GP-M)是在需要能量时(如运动时)降解糖原的关键酶,其活性在突变体肌肉中显著降低。此外,用百草枯(一种超氧化物生成物)处理后,正常肌肉切片上的 GP-M 活性也降低了。与此相反,使用抗氧化剂处理可逆转突变体小鼠的 GP-M 活性和运动障碍,这表明 GP-M 活性受氧化还原平衡的可逆调节。这些结果表明,线粒体氧化还原平衡的维持通过 GP-M 活性调节糖原代谢。
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来源期刊
Antioxidants
Antioxidants Biochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍: Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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