Mitochondria are double-membrane organelles in most eukaryotic cells with prokaryotic origins. The human mitochondrial genome is 16,569 bp and encodes 37 genes, including 13 core proteins of the respiratory complexes I-IV, essential for oxidative phosphorylation (OXPHOS).
Mutations in mitochondrial DNA (mtDNA) or nuclear genes encoding mitochondrial proteins can disrupt ATP synthesis, leading to disorders like mitochondrial myopathy and Leigh syndrome. For example, the m.3243A>G mutation in the MT-TL1 gene is linked to MELAS syndrome, impairing OXPHOS by affecting tRNA structure or function. Another mutation, m.1555A>G, is associated with hearing loss.
Structural variations in mitochondria have been linked to ageing and diseases such as Alzheimer’s and cancer, as these changes may affect mitochondrial function. Mitochondrial distribution varies across cells, with a threshold effect on human traits, making accurate genetic diagnosis challenging. Human migration and selection pressures have led to diverse mitochondrial haplotypes and phylogenies.
There is no comprehensive analysis of the roles of mitochondrial structural variations and haplotypes in disease susceptibility and ageing. Our research will examine the relationships between mitochondrial haplotypes, ageing/disease phenotypes, and mitochondrial variants, and explore the influence of lifestyle and sex on mitochondrial structural variation.
