Figure1. The mitochondrial network in a cultured muscle cell.
Mitochondria are the engine of eukaryotic cellular metabolism. Mitochondria sustain cells with a continuous supply of ATP, replenish metabolic intermediates, and coordinate metabolic flux with numerous aspects of cellular biology. Accordingly, mitochondrial dysfunction is a root cause of devastating diseases, including cancer, neurodegeneration, and diabetes.
The Taylor Lab is interested in the molecular mechanisms regulating mitochondrial function and their relationship to disease. Our research program is multidisciplinary, utilizing genetic, biochemical, cellular, and physiological experimental approaches. We have additional interest in problems related to skeletal muscle function and diabetes.
Our current research projects focus on novel proteins important for mitochondrial function. The first is on VMS1, a protein that recruits components of the ubiquitin proteasome system to stressed mitochondria to extract damaged proteins for presentation to the proteasome, thereby maintaining mitochondrial protein quality. Thus, VMS1 may be relevant to any disease involving progressive mitochondrial failure. The second is on the mitochondrial pyruvate carrier (MPC), which Dr. Taylor recently co-discovered. Mitochondrial pyruvate uptake is critical for ATP production by the TCA cycle and for generating the synthetic intermediates supporting fat, protein, and carbohydrate metabolism. Therefore, MPC function is essential for normal physiology and its disruption causes diverse and severe metabolic abnormalities. We are interested in discovering the mechanisms regulating the function of the MPC molecule.
Figure 2. In the cytosol a single molecule of glucose is oxidized by glycolysis to two molecules of pyruvate. Pyruvate passively diffuses through pores in the outer mitochondrial membrane (OMM) but requires transit through the mitochondrial pyruvate carrier (MPC) to cross the inner mitochondrial membrane (IMM) and reach the mitochondrial matrix. After reaching the matrix, pyruvate can be oxidized to CO2 by the TCA cycle to produce ATP and extract most of the energy available in the original glucose molecule. Mitochondrial pyruvate is also the major substrate supporting the anabolic processes of gluconeogenesis and lipogenesis.
- Fraternal Order of Eagles Diabetes Research Center (FOEDRC)
- University of Iowa Obesity Research and Education Initiative (OREI)
- Holden Comprehensive Cancer Center (HCCC)
- University of Iowa Cardiovascular Research Center (CVC)
- Molecular and Cellular Biology Program (MCB)
- Medical Scientist Training Program (MSTP)