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<p>During the conversion of fibroblasts into induced pluripotent stem cells (iPSCs), cellular metabolism shifts from oxidative phosphorylation toward glycolysis; however, how functional and structural mitochondrial adaptations are coordinated remains incompletely understood. Here, we examined selected aspects of mitochondrial function, targeted gene expression, and ultrastructure in fibroblasts and iPSCs derived from healthy donors and patients with osteogenesis imperfecta (OI). Targeted gene expression analysis was performed in all four cell types, while functional and ultrastructural assays focused on OI-derived cells. Flow cytometry revealed reduced mitochondrial mass and reactive oxygen species (ROS) levels in iPSCs compared with fibroblasts. Mitochondrial membrane potential showed modestly reduced fluorescence depending on the probe used. Quantitative transmission electron microscopy demonstrated internal mitochondrial reorganization in iPSCs, including altered morphology and simplified cristae architecture, despite preservation of overall membrane integrity. These findings indicate that reprogramming induces coordinated functional downscaling and structural remodeling of mitochondria. Furthermore, differential expression of matrix metalloproteinases suggests that extracellular matrix remodeling accompanies metabolic adaptation during reprogramming.</p>

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Functional suppression accompanies internal mitochondrial reorganization during cellular reprogramming

  • 期刊论文

  • 发表日期：

    2026年4月20日

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  • N. Diak,
  • L. Sieroń,
  • K. Janelt,
  • L. Chajec,
  • A. Fus-Kujawa,
  • A. Dziedzic-Kowalska,
  • A. Trybus,
  • K. Raszczok,
  • K. Bajdak-Rusinek

摘要

During the conversion of fibroblasts into induced pluripotent stem cells (iPSCs), cellular metabolism shifts from oxidative phosphorylation toward glycolysis; however, how functional and structural mitochondrial adaptations are coordinated remains incompletely understood. Here, we examined selected aspects of mitochondrial function, targeted gene expression, and ultrastructure in fibroblasts and iPSCs derived from healthy donors and patients with osteogenesis imperfecta (OI). Targeted gene expression analysis was performed in all four cell types, while functional and ultrastructural assays focused on OI-derived cells. Flow cytometry revealed reduced mitochondrial mass and reactive oxygen species (ROS) levels in iPSCs compared with fibroblasts. Mitochondrial membrane potential showed modestly reduced fluorescence depending on the probe used. Quantitative transmission electron microscopy demonstrated internal mitochondrial reorganization in iPSCs, including altered morphology and simplified cristae architecture, despite preservation of overall membrane integrity. These findings indicate that reprogramming induces coordinated functional downscaling and structural remodeling of mitochondria. Furthermore, differential expression of matrix metalloproteinases suggests that extracellular matrix remodeling accompanies metabolic adaptation during reprogramming.