Mitochondrial Cristae Remodeling in HeLa Cervical Carcinoma Cells Under Hypoxia-Induced OPA1 Oligomerization: A Quantitative Ultrastructural Analysis

Abstract

Mitochondrial cristae architecture is a critical determinant of oxidative phosphorylation efficiency and apoptotic regulation. This study examines hypoxia-driven OPA1 oligomerization and its downstream effects on cristae junction width, respiratory supercomplex assembly, and cytochrome c sequestration in HeLa cervical carcinoma cells. Using a combination of focused ion beam scanning electron microscopy (FIB-SEM), proximity ligation assay (PLA), and Blue Native PAGE, we quantified ultrastructural remodeling events under 1% O₂ conditions over 6–48 hours. Our data demonstrate that sustained hypoxia induces a statistically significant narrowing of cristae junctions (p < 0.001) concurrent with elevated OPA1 high-molecular-weight oligomer formation and enhanced OXPHOS supercomplex I+III₂+IV stoichiometry. These findings establish a mechanistic link between inner mitochondrial membrane fusion dynamics and metabolic adaptation in hypoxic tumor microenvironments, with implications for mitochondria-targeted cancer therapeutics.