Morphological alterations of peridroplet mitochondria in human liver biopsy

Mitochondrial dysfunction and the accumulation of lipid droplets (LD) contribute to the pathogenesis of liver diseases. Mitochondria bound to LD, termed peridroplet mitochondria (PDM), form a subpopulation with distinct functions compared to cytoplasmic mitochondria (CM). In this first in vivo human liver study, we aimed to investigate the morphological differences between PDM and CM and to assess their associations with clinical parameters. Our analysis of mitochondrial ultrastructure using transmission electron microscopy images of human liver biopsies showed that CM were significantly smaller, more spherical, and solid, whereas PDM were larger and more elongated. Overall, PDM exhibited more uniform morphology, while CM displayed disease-specific morphological alterations. CM were associated with serum liver enzyme levels and high-density lipoprotein cholesterol, suggesting sensitivity to liver stress and a potential role in liver cholesterol transport. In contrast, PDM were associated with serum triglyceride levels, indicating a role in lipid metabolism. Total PDM and LD counts showed a positive correlation, reinforcing their close functional relationship. These findings show that PDM and CM represent distinct mitochondrial subpopulations with unique morphologies and differing associations with hepatic pathophysiological pathways, which highlights the significance of LD interactions in contributing to mitochondrial heterogeneity.