Human Biallelic MFN2 Mutations Induce Mitochondrial Dysfunction, Upper Body Adipose Hyperplasia, and Suppression of Leptin Expression

The study investigated the effects of biallelic MFN2 mutations on mitochondrial function and adipose tissue distribution, revealing severe mitochondrial disruption in adipocytes and metabolic abnormalities in patients. Researchers found normal mitochondrial morphology in dermal fibroblasts from three patients but noted elevated blood lactate levels and abnormal mitochondrial protein expression in affected adipose tissues, indicating tissue-selective mitochondrial dysfunction. The study also observed upper body adipose hyperplasia and lower limb lipodystrophy, though the mechanisms were unclear. Reviewers suggested revisions for clarity and additional experiments, and the authors agreed to address these concerns and emphasize the unique aspects of their findings. Further research with more patients was recommended.