Despite diurnal fluctuations in nutrient availability, hepatocytes adjust their metabolic output to maintain glucose and lipid homeostasis. At the heart of this metabolic adaptation are mitochondria, where fuel selection and oxidation occur. Mitochondria demonstrate remarkable plasticity to respond appropriately to the environmental demands placed on them. This metabolic flexibility is vital for cell and organ function in normal physiology, and its impairment can result in disease. The Porat-Shliom lab is interested in fundamental questions related to mitochondrial biology in the liver. How are mitochondrial structure and function regulated? What are the environmental cues/stressors that induce these mitochondrial alterations? And, in turn, how are mitochondrial structure and function disrupted in human disease?

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To address these questions, we leverage our expertise in Intravital microscopy, using advanced light microscopy modalities and precise surgical procedures to examine biological processes in live, anesthetized animals (Stefkovich et al. 2021). In combination with mouse genetics, pharmacological perturbation and diet-induced metabolic stress, we study mitochondrial responses in intact liver tissue. These studies offer valuable insights into the healthy physiology of mitochondrial function and plasticity, as well as provide the foundation to understand the drivers of mitochondrial dysfunction in liver disease.

We are particularly interested in Nonalcoholic fatty liver disease (NAFLD), which affects 1 in 4 people worldwide and is one of the leading causes of liver cancer. Patients suffering from NAFLD have an impaired ability for the liver to switch between the feeding and fasting state to control glucose homeostasis due in part to defective mitochondria. Ultimately, our studies will lead to novel therapeutic avenues and clinical applications in cancer research.