Approaches and challenges in identifying, quantifying, and manipulating dynamic mitochondrial genome variations

Mitochondria, the cellular powerhouses, possess their own unique genetic system, including replication, transcription, and translation. Studying these processes is crucial for comprehending mitochondrial disorders, energy production, and their related diseases. Over the past decades, various approaches have been applied in detecting and quantifying mitochondrial genome variations with also the purpose of manipulation of mitochondria or mitochondrial genome for therapeutics. Understanding the scope and limitations of above strategies is not only fundamental to the understanding of basic biology but also critical for exploring disease-related novel target(s), as well to develop innovative therapies. Here, this review provides an overview of different tools and techniques for accurate mitochondrial genome variations identification, quantification, and discuss novel strategies for the manipulation of mitochondria to develop innovative therapeutic interventions, through combining the insights gained from the study of mitochondrial genetics with ongoing single cell omics combined with advanced single molecular tools.