03/04/2026
OXPHOS Lifecycle and Aging: Where Things Go Wrong👇
✅OXPHOS production starts with gene expression:
Subunits of the mitochondrial respiratory complexes come from both nuclear DNA (translated in the cytosol) and mtDNA (translated inside mitochondria). These components must be tightly coordinated.
✅Import and maturation of proteins:
Nuclear-encoded proteins are imported into mitochondria via membrane translocases (TOM/TIM) in a ΔΨm-dependent manner. They are then processed, folded, and matured with the help of chaperones and proteases.
✅Assembly of functional complexes:
Subunits are assembled into respiratory complexes within the inner membrane, aided by assembly factors. These complexes can further organize into supercomplexes for efficient energy production.
✅Quality control and turnover:
Damaged or misfolded proteins are repaired or degraded by mitochondrial proteases, ensuring proper function and preventing accumulation of defective components.
✅What changes with aging?
✅Disrupted gene expression coordination:
Aging can impair the balance between nuclear and mitochondrial gene expression, leading to inefficient production of OXPHOS components.
✅Accumulation of mtDNA mutations:
Mutations in mtDNA increase over time, producing defective subunits that destabilize respiratory complexes.
✅Impaired protein import and assembly:
Reduced membrane potential (ΔΨm) and altered processing can limit protein import and proper complex assembly.
✅Defective quality control:
Protein turnover and surveillance become less efficient, leading to protein aggregation or excessive degradation.
✅Altered mitochondrial function:
Changes in metabolic environment can shift OXPHOS activity, affecting ROS levels, cofactor availability, and electron flow.
💡almonowicz H, Szczepanowska K
The fate of mitochondrial respiratory complexes in aging
Trends in Cell Biology, 2025; 35, 955-970