bims-smemid Biomed News
on Stress metabolism in mitochondrial dysfunction
Issue of 2026–04–19
two papers selected by
Deepti Mudartha, The International Institute of Molecular Mechanisms and Machines
  1. Biallelic variants in CHCHD4 are associated with combined OXPHOS defect leading to mitochondrial disease.
  2. Protocol for metabolite extraction and sample preparation from primary astrocytes for mass spectrometry-based metabolomic analysis.
  1. HGG Adv. 2026 Apr 13. pii: S2666-2477(26)00055-2. [Epub ahead of print] 100615
    Biallelic variants in CHCHD4 are associated with combined OXPHOS defect leading to mitochondrial disease.
    Matthieu Mantecon, Cerina Chhuon, Kevin Roger, Ida Chiara Guerrera, Christine Bole, Patrick Nitschke, Claire-Marie Dufeu-Bérat, Margaret Ashcroft, Robert W Taylor, Nathalie Boddaert, Agnès Rötig.
      Mitochondrial disorders show remarkable clinical and genetic heterogeneity, and result from variants in either mitochondrial- or nuclear-encoded genes. CHCHD4 is a component of the mitochondrial import and assembly pathway that imports small cysteine-containing substrates. We report a pediatric patient with biallelic CHCHD4 variants who presented with severe neurological regression and early death. Western blot analysis showed decreased levels of CHCHD4 and diminished assembly of complexes I and IV in his fibroblasts. To demonstrate that CHCHD4 variants were responsible for the observed biochemical phenotype, we overexpressed wild-type CHCHD4 in control and subject fibroblasts, restoring levels of complex I and IV proteins and the associated assembly defects Proteomic studies pointed to electron transport and complex I biogenesis as the main dysregulated pathways and showed a severe loss of several complex I and IV proteins and/or assembly factors rescued by overexpression of wild-type CHCHD4. CHCHD4 has numerous targets and interacting factors and is involved in the export of iron-sulfur clusters synthesized inside mitochondria. Surprisingly, few of these interacting factors or non-mitochondrial functions were impacted by the observed CHCHD4 defect. In conclusion, our work establishes CHCHD4 deficiency as a cause of dysregulated mitochondrial protein import resulting in a severe neurological condition.
    DOI:  https://doi.org/10.1016/j.xhgg.2026.100615
  2. STAR Protoc. 2026 Apr 10. pii: S2666-1667(26)00144-9. [Epub ahead of print]7(2): 104491
    Protocol for metabolite extraction and sample preparation from primary astrocytes for mass spectrometry-based metabolomic analysis.
    Ya-Gin Chang, Gong-Min Lin, Chih-Yu Lin, Yijuang Chern.
      Astrocytes play essential roles in supporting neuronal function, particularly through the regulation of brain energy metabolism. In response to physiological and pathological stimuli, astrocytes dynamically adjust their metabolic pathways and energy output. Here, we present a protocol for metabolite extraction and sample preparation from primary astrocytes for mass spectrometry analysis. We describe steps for integrating astrocyte culture and liquid chromatography-mass spectrometry (LC-MS) metabolite analysis to enable reproducible profiling of astrocytic energy metabolism under different experimental conditions. For complete details on the use and execution of this protocol, please refer to Chang et al.1.
    Keywords:  Cell culture; Metabolomics; Neuroscience; Protocols in Metabolomics and Lipidomics
    DOI:  https://doi.org/10.1016/j.xpro.2026.104491
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