Iain Scott, PhD
Assistant Professor of Medicine

Dr. Scott
Dr. Scott is a member of Division of Cardiology, Department of Medicine, University School of Medicine.

Office Location:
BST 1253E
200 Lothrop Street
Pittsburgh, PA 15261
Contact Information:
Office Telephone: 412) 648-7691
Fax: (412) 648-5980
E-Mail: scotti2@upmc.edu


  • B.Sc. (Hons) - University of St. Andrews, 2002
  • Ph.D. - University of St. Andrews, 2006
  • Research Interests

    The general focus of my laboratory is mitochondrial metabolism and bioenergetics, and the role that mitochondrial dysfunction can play in the pathophysiology of human diseases.

    Mitochondria are ubiquitous organelles, playing a vital role in bioenergetics, metabolite biosynthesis and overall cellular homeostasis. Their functional activity needs to be tightly regulated, as shown by the growing number of pathologies in which mitochondrial dysfunction is recognized as either a causative or compounding factor. Mitochondria are highly susceptible to environmental stresses, with over-nutrition being a particular problem in the developed world. A high caloric intake leads to a surge in available acetyl-CoA (the final breakdown product of fats, carbohydrates and proteins in the mitochondria), which cannot be efficiently utilized for energetic or synthetic purposes. This excess acetyl-CoA can instead be used as the substrate for acetylation (a post-translational modification of lysine residues), which acts to reduce the activity of a vast number of mitochondrial metabolic enzymes.

    Our work examines the role played by lysine acetylation in the development and progression of metabolic disorders such as diabetic cardiomyopathy, heart failure, and non-alcoholic fatty liver disease (NAFLD).

    Selected Publications

    View Dr. Scott's publications on PubMed

    1. Thapa D, Zhang M, Manning JR, Guimar„es DA, Stoner MW, O'Doherty RM, Shiva S, Scott I. Acetylation of mitochondrial proteins by GCN5L1 promotes enhanced fatty acid oxidation in the heart. American Journal of Physiology - Heart and Circulatory Physiology (2017) 311: H265-H274 (PMID: 28526709)
    2. Wang L, Scott I, Zhu L, Wu K, Han K, Chen Y, Gucek, M, Sack MN. GCN5L1 modulates cross-talk between mitochondria and cell signaling to regulate FoxO1 stability and gluconeogenesis. Nature Communications (2017) 8: 523 (PMID 28900165)
    3. Thapa D, Stoner MW, Zhang M, Xie B, Manning JR, Guimaraes DA, Shiva S, Jurczak MJ, Scott I. Adropin Regulates Pyruvate Dehydrogenase in Cardiac Cells via a Novel GPCR-MAPK-PDK4 Signaling Pathway. Redox Biology (2018) 18: 25-32 (PMID: 29909017)
    4. Wu K, Wang L, Chen Y, Pirooznia M, Singh K, Walde S, Kehlenbach RH, Scott I, Gucek M, Sack MN. GCN5L1 interacts with alpha-TAT1 and RanBP2 to regulate hepatic alpha-tubulin acetylation and lysosome trafficking. Journal of Cell Science (2018) 131: jcs221036 (PMID: 30333138)
    5. Thapa D, Wu K, Stoner MW, Xie, B, Zhang M, Manning JR, Lu Z, Li JH, Chen Y, Harmon D, O'Doherty RM, Gucek, M, Playford MP, Mehta NN, Sack MN, Scott I. The protein acetylase GCN5L1 modulates hepatic fatty acid oxidation activity via acetylation of the mitochondrial ?-oxidation enzyme HADHA. Journal of Biological Chemistry (2018) 293:17676-17684 (PMID: 30323061)
    6. Manning JR, Thapa D, Zhang M, Stoner MW, Traba J, McTiernan CF, Cory C, Shiva S, Sack MN, Scott I. Cardiac-specific deletion of GCN5L1 restricts recovery from ischemia-reperfusion injury. Journal of Molecular and Cellular Cardiology (2019) 129: 69-78 (PMID: 30776374)
    7. Thapa D, Xie, B, Zhang M, Stoner MW, Manning JR, Huckestein BR, Edmunds LR, Mullet SJ, McTiernan CF, Wendell SG, Jurczak MJ, Scott I. Adropin Treatment Restores Cardiac Glucose Oxidation in Pre-Diabetic Obese Mice. Journal of Molecular and Cellular Cardiology (2019) 129: 174-178 (PMID: 30822408)
    8. Thapa D, Xie, B, Manning JR, Zhang M, Stoner MW, Huckestein BR, Edmunds LR, Zhang X, Dedousis NL, O'Doherty RM, Jurczak MJ, Scott I. Adropin reduces blood glucose levels in mice by limiting hepatic glucose production. Physiological Reports (2019) 7: e14043 (PMID: 31004398)
    9. Thapa D, Zhang M, Manning JR, Guimaraes DA, Lai Y-C, Stoner MW, Shiva S, Scott I. Loss of GCN5L1 in cardiac cells limits mitochondrial respiratory capacity under hyperglycemic conditions. Physiological Reports (2019) 7: e14054 (PMID: 31033247)
    10. Manning JR, Thapa D, Zhang M, Stoner MW, Traba J, Cory C, Shiva S, Sack MN, Scott I. Loss of GCN5L1 in cardiac cells disrupts glucose metabolism and promotes cell death via reduced Akt/mTORC2 signaling. Biochemical Journal (2019) 476: 1713-1724 (PMID: 31138772)