Analyses of mitochondrial metabolism in diseases: a review on C magnetic resonance tracers

Metabolic diseases such as obesity, type 2 diabetes, and cardiovascular diseases have become a global health concern due to their widespread prevalence and profound impact on life expectancy, healthcare expenditures, and the overall economy. Devising effective treatment strategies and management plans for these diseases requires an in-depth understanding of the pathophysiology of the metabolic abnormalities associated with each disease. Mitochondrial dysfunction is intricately linked to a wide range of metabolic abnormalities and is considered an important biomarker for diseases. However, assessing mitochondrial functions in viable tissues remains a challenging task, with measurements of oxygen consumption rate (OCR) and ATP production being the most widely accepted approaches for evaluating the health of mitochondria in tissues. Measurements of cellular metabolism using carbon-13 (or 13 C) tracers have emerged as a viable method for characterizing mitochondrial metabolism in a variety of organelles ranging from cultured cells to humans. Information on metabolic activities and mitochondrial functions can be obtained from magnetic resonance (MR) analyses of 13 C-labeled metabolites in tissues and organs of interest. Combining novel 13 C tracer technologies with advanced analytical and imaging tools in nuclear magnetic resonance spectroscopy (NMR) and magnetic resonance imaging (MRI) offers the potential to detect metabolic abnormalities associated with mitochondrial dysfunction. These capabilities would enable accurate diagnosis of various metabolic diseases and facilitate the assessment of responses to therapeutic interventions, hence improving patient health and optimizing clinical outcomes. This review discusses 13 C NMR approaches for analyzing mitochondrial metabolism in tissues.