Abstract
Mitochondrial diseases encompass a heterogeneous group of disorders with a wide range of clinical manifestations, most classically resulting in neurological, muscular, and metabolic abnormalities, but having the potential to affect any organ system. Over the years, substantial progress has been made in identifying and characterizing various biomarkers associated with mitochondrial diseases. This review summarizes the current knowledge of mitochondrial biomarkers based on a literature review and discusses the evidence behind their use in clinical practice. A total of 13 biomarkers were thoroughly reviewed including lactate, pyruvate, lactate:pyruvate ratio, creatine kinase, creatine, amino acid profiles, glutathione, malondialdehyde, GDF-15, FGF-21, gelsolin, neurofilament light-chain, and circulating cell-free mtDNA. Most biomarkers had mixed findings depending on the study, especially when considering their utility for specific mitochondrial diseases versus mitochondrial conditions in general. However, in large biomarker comparison studies, GDF-15 followed by FGF-21, seem to have the greatest value though they are still not perfect. As such, additional studies are needed, especially in light of newer biomarkers that have not yet been thoroughly investigated. Understanding the landscape of biomarkers in mitochondrial diseases is crucial for advancing early detection, improving patient management, and developing targeted therapies.