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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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.