Alterations in mitochondrial metabolism and bioenergetics have been implicated in a wide array of chronic disease states and aging. We are attempting to understand the ways in which mitochondrial function is altered in diseases of overnutrition such as obesity and type 2 diabetes and how exercise can confer protection against these conditions. With aging and under states of chronic nutrient overload, skeletal muscle mitochondria display a preference for fat oxidation at the expense of other substrates whereas exercise training mitigates this phenotype (1,2,3,4). From these observations, we are trying to understand the consequences of this nutrient-induced "metabolic inflexibility" on the whole organism, skeletal muscle physiology and function, and mitochondrial health. In longstanding collaborations with the laboratory of Debbie Muoio, we have developed expertise in the area of mitochondrial and skeletal muscle physiology and metabolism, exercise, age-related metabolic decline, as well as the design and interpretation of mass spectrometry-based metabolic profiling experiments (5,6,7,8).
My current work focuses on molecular connections between mitochondrial health and metabolic control, with a particular interest in understanding the contribution of lipid dysregulation and mitochondrial dysfunction to age-related decline of skeletal muscle function. We utilize a comprehensive array of state-of-the-art tools to assess mitochondrial metabolism and bioenergetic function including but not limited to high resolution respirometry, cellular O2 flux analysis, radiolabeled substrates, stable isotope tracers, mass-spectrometry based metabolic profiling and whole-animal calorimetry. This battery of tools allows us to evaluate metabolic status in animals, cell culture systems, permeabilized muscle fibers and isolated mitochondria. Recently, exciting collaborative work with the Department of Biomedical Engineering is focused on understanding mitochondrial metabolism in bioengineered 3d skeletal and cardiac muscle cultures with the aim of improving functional outcomes relevant to tissue regeneration and transplant (9).