Identification of determinants for variability in mitochondrial biochemical complex activities

IF 3.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et Biophysica Acta-Bioenergetics Pub Date : 2025-03-09 DOI:10.1016/j.bbabio.2025.149553

Sandra Monica Bach de Courtade , Marte Eikenes , Ying Sheng , Tuula A. Nyman , Yngve Thomas Bliksrud , Katja Scheffler , Lars Eide

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引用次数: 0

Abstract

Diagnostics of mitochondrial disease requires a combination of clinical evaluations and biochemical characterization. However, the large normal variation in mitochondrial complex activity limits the precision of biochemical diagnostics. Thus, identifying factors that contribute to such variations could enhance diagnostic accuracy. In comparison, inbred mice demonstrate much less variations in brain mitochondrial activity, but a clear reduction with age. Interestingly, pretreatment of mouse brain mitochondria with the detergent dodecyl maltoside abolishes the reduction. We therefore postulated that DDM pretreatment could be valuable tool for distinguishing between variations caused by posttranslational modifications and those caused by genetic heterogeneity.

In this study, we evaluated the effects of age, DDM sensitivity, oxidative damage and single nucleotide polymorphism on biochemical complex activity and the proteome of human muscle mitochondria, which serve as reference standards for mitochondrial diagnostics. Our results indicate that mtDNA variants are the primary contributors to the diversity in biochemical activity in human muscle mitochondria from healthy individuals.

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鉴定线粒体生化复合体活动变异的决定因素

线粒体疾病的诊断需要结合临床评估和生化表征。然而，线粒体复合体活性的巨大正常变异限制了生化诊断的准确性。因此，识别导致这些变化的因素可以提高诊断的准确性。相比之下，近亲繁殖的老鼠大脑线粒体活动的变化要小得多，但随着年龄的增长明显减少。有趣的是，用洗涤剂十二烷基麦芽糖苷预处理小鼠脑线粒体可以消除这种还原。因此，我们假设DDM预处理可能是区分翻译后修饰引起的变异和遗传异质性引起的变异的有价值的工具。在本研究中，我们评估了年龄、DDM敏感性、氧化损伤和单核苷酸多态性对人类肌肉线粒体生化复合物活性和蛋白质组的影响，为线粒体诊断提供参考标准。我们的研究结果表明，mtDNA变异是健康个体人类肌肉线粒体生化活性多样性的主要贡献者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et Biophysica Acta-Bioenergetics 生物-生化与分子生物学

CiteScore

9.50

自引率

7.00%

发文量

363

审稿时长

92 days

期刊介绍： BBA Bioenergetics covers the area of biological membranes involved in energy transfer and conversion. In particular, it focuses on the structures obtained by X-ray crystallography and other approaches, and molecular mechanisms of the components of photosynthesis, mitochondrial and bacterial respiration, oxidative phosphorylation, motility and transport. It spans applications of structural biology, molecular modeling, spectroscopy and biophysics in these systems, through bioenergetic aspects of mitochondrial biology including biomedicine aspects of energy metabolism in mitochondrial disorders, neurodegenerative diseases like Parkinson''s and Alzheimer''s, aging, diabetes and even cancer.