Biochimica et biophysica acta. Bioenergetics. 2025 Mar 9:149553. doi: 10.1016/j.bbabio.2025.149553 Q23.42024

Identification of determinants for variability in mitochondrial biochemical complex activities

确定影响线粒体生化复合物活性变异的决定因素翻译改进

Sandra Monica Bach de Courtade¹, Marte Eikenes², Ying Sheng³, Tuula A Nyman⁴, Yngve Thomas Bliksrud⁵, Katja Scheffler⁶, Lars Eide⁷

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作者单位

¹ Department of Medical Biochemistry, Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway. Electronic address: sanbac@ous-hf.no.

² Department of Medical Biochemistry, University of Oslo, Sognsvannsveien 20, 0372 Oslo, Norway. Electronic address: marte.eikenes@medisin.uio.no.

³ Department of Medical Genetics, Oslo University Hospital, Kirkeveien 166, 0450 Oslo, Norway. Electronic address: ying.sheng@medisin.uio.no.

⁴ Department of Immunology and transfusion medicine, University of Oslo and University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway. Electronic address: tuula.nyman@medisin.uio.no.

⁵ Department of Medical Biochemistry, Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway. Electronic address: ybliksru@ous-hf.no.

⁶ Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology (NTNU), and Department of Neurology and Clinical Neurophysiology, University Hospital Trondheim, Edvard Griegs Gate 8, Trondheim, Norway. Electronic address: katja.scheffler@ntnu.no.

⁷ Department of Medical Biochemistry, Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway; Department of Medical Biochemistry, University of Oslo, Sognsvannsveien 20, 0372 Oslo, Norway. Electronic address: lars.eide@medisin.uio.no.

DOI: 10.1016/j.bbabio.2025.149553 PMID: 40068806

摘要 Ai翻译

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.

Keywords: Dodecyl maltoside; ETC; Heteroplasmy; Mitochondrial function; mtDNA damage.

Keywords：activities variability; Identification determinants

关键词：线粒体生物化学复合物; 活性变异性; 识别决定因素