In nucleated eukaryotic cells, mitochondria are active organelles that are constantly present and serve a variety of metabolic tasks, including cellular ATP production. Oxidative phosphorylation, also known as OXPHOS. Five transmembrane respiratory chain enzyme complexes (RC) make up the OXPHOS mechanism. Mitochondrial disorders (mtD) are caused by defective OXPHOS. At least in part, the RC dual genetic control (nuclear DNA [nDNA] and mitochondrial DNA [mtDNA]) and the intricate interplay between the two genomes are responsible for the extraordinary phenotypic and genetic variety of mtD. The current clinical practise for investigating mtD essentially involves a multifaceted approach including clinical assessment, metabolic screening, imaging, pathological, biochemical, and functional testing to guide molecular genetic analysis, despite the growing use of Next-Generation Sequencing (NGS) and various -omics platforms in unravelling novel mtD genes and pathomechanisms. This review discusses the entire spectrum of muscle pathology, including genotype-phenotype relationships in adult and paediatric mtD, the contribution of immunodiagnostics to the understanding of some of the patho-mechanisms underlying the canonical aspects of mtD, and current developments in the field of diagnostics.
