Scholarlink

Background <p>Widespread neuronal mitochondrial complex I (CI) deficiency was recently reported to be a characteristic in a subgroup of individuals with idiopathic Parkinson’s disease (PD). Here, we sought to determine whether a CI-deficient subgroup could be discerned using clinically accessible muscle biopsies. We further hypothesized that the inconsistency of previous findings of mitochondrial respiratory impairment in PD muscle may be due to interindividual variation, with respiratory deficiency only occurring in a subgroup of cases.</p> Methods <p>Using a cross-sectional design, vastus lateralis needle biopsies were collected from 83 individuals with PD and 29 neurologically healthy controls and analyzed by immunohistochemistry for CI and complex IV (CIV), cytochrome c oxidase/succinate dehydrogenase (COX/SDH) histochemistry, and spectrophotometric activity assays of complexes I–IV. Mitochondrial DNA (mtDNA) copy number, deletions, and point variation were analyzed in single muscle fibers and bulk biopsy samples.</p> Results <p>We show that PD muscle exhibits reduced CI activity at the group level, with 9% of cases falling below two standard deviations of the control group. In contrast, the activities of CII–CIV are not significantly different between the PD and control groups. No quantitative change of CI or CIV is detected, and the observed functional CI deficiency is not associated with mtDNA abnormalities.</p> Conclusions <p>Our findings support the existence of a PD subpopulation characterized by CI pathology in skeletal muscle and suggest that stratification by extra-neural mitochondrial dysfunction may be informative for selecting individuals for clinical trials.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Mitochondrial complex I deficiency occurs in skeletal muscle of a subgroup of individuals with Parkinson’s disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月27日

查看全文
  • Simon Ulvenes Kverneng,
  • Kjersti Eline Stige,
  • Haakon Berven,
  • Sepideh Mostafavi,
  • Katarina Lundervold,
  • Michele Brischigliaro,
  • Brage Brakedal,
  • Geir Olve Skeie,
  • Irene Hana Flønes,
  • Lilah Toker,
  • Erika Fernandez-Vizarra,
  • Ragnhild Eide Skogseth,
  • Kristoffer Haugarvoll,
  • Yamila N. Torres Cleuren,
  • Christian Dölle,
  • Gonzalo S. Nido,
  • Charalampos Tzoulis

摘要

Background

Widespread neuronal mitochondrial complex I (CI) deficiency was recently reported to be a characteristic in a subgroup of individuals with idiopathic Parkinson’s disease (PD). Here, we sought to determine whether a CI-deficient subgroup could be discerned using clinically accessible muscle biopsies. We further hypothesized that the inconsistency of previous findings of mitochondrial respiratory impairment in PD muscle may be due to interindividual variation, with respiratory deficiency only occurring in a subgroup of cases.

Methods

Using a cross-sectional design, vastus lateralis needle biopsies were collected from 83 individuals with PD and 29 neurologically healthy controls and analyzed by immunohistochemistry for CI and complex IV (CIV), cytochrome c oxidase/succinate dehydrogenase (COX/SDH) histochemistry, and spectrophotometric activity assays of complexes I–IV. Mitochondrial DNA (mtDNA) copy number, deletions, and point variation were analyzed in single muscle fibers and bulk biopsy samples.

Results

We show that PD muscle exhibits reduced CI activity at the group level, with 9% of cases falling below two standard deviations of the control group. In contrast, the activities of CII–CIV are not significantly different between the PD and control groups. No quantitative change of CI or CIV is detected, and the observed functional CI deficiency is not associated with mtDNA abnormalities.

Conclusions

Our findings support the existence of a PD subpopulation characterized by CI pathology in skeletal muscle and suggest that stratification by extra-neural mitochondrial dysfunction may be informative for selecting individuals for clinical trials.