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Department of Medicine

Department of Medicine

  Division of Cardiology

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photo Iain Scott, PhD

Assistant Professor

Email: scotti2@upmc.edu

Phone: 412-648-7691

Contact
Office: E1253 BST
200 Lothrop Street
Pittsburgh, PA 15261
 
Phone: 412-648-7691
Fax:
E-mail: scotti2@upmc.edu
Education and Training
Education
PhD, University of St. Andrews (UK)
Research Interest
Mitochondria are ubiquitous organelles, playing a vital role in bioenergetics, metabolite biosynthesis and overall cellular homeostasis. Their activity needs to be tightly regulated, as evidenced by the growing number of pathologies in which mitochondrial dysfunction is a causative factor. Mitochondria are highly susceptible to environmental stresses, with overnutrition 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 utilized for energetic or synthetic purposes. This excess acetyl-CoA is instead 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 focuses on the intrinsic mechanisms that regulate mitochondrial protein acetylation, and how this fundamental alteration affects organelle function at the cellular and tissue level. In particular, we are interested in the coordination between acetylation levels and mitophagy, a quality control mechanism that mediates the removal of dysfunctional mitochondrial organelles. We have recently discovered that GCN5L1, a mitochondrial protein that promotes lysine acetylation, regulates the transcriptional machinery of mitophagy. Our future work will aim to elucidate the pathways that link nutritional inputs, GCN5L1-mediated lysine acetylation, and mitochondrial quality control systems. These findings will then be translated into studies involving metabolically-relevant disease models, such as heart failure and diabetes, in order to achieve a better understanding of the role played by dysfunctional mitochondria in these processes.
Educational Interest
Member, Molecular Pharmacology Graduate Training Program
Member, Cell and Molecular Pathology Graduate Training Program
Lecturer, Fundamentals of Bench Research (CLRES2700)
Module Leader and Lecturer, Molecular Pathobiology (MSCMP 2740) – Congestive Heart Failure
Publications
For my complete bibliography, Click Here.
Selected Publications:
Stoner MW, Thapa D, Zhang M, Gibson GA, Calderon MJ, St. Croix CM, Scott I. a-Lipoic Acid Promotes a-Tubulin Hyperacetylation and Blocks the Turnover of Mitochondria through Mitophagy. Biochemical Journal. 2016; 473: 1821-30.
Scott I, Webster BR, Chan CK, Okonkwo JU, Han K, Sack MN. GCN5-like protein 1 (GCN5L1) controls mitochondrial content through coordinated regulation of mitochondrial biogenesis and mitophagy. Journal of Biological Chemistry. 2014; 289: 2864-72.
Webster BR, Scott I, Stevens MV, Lu Z, Li JH, Han K, Sack MN. Restricted mitochondrial protein acetylation initiates mitochondrial removal by autophagy. Journal of Cell Science. 2013; 126: 4843-49.
Scott I, Webster BR, Li JH, Sack MN. Identification of a molecular component of the mitochondrial acetyltransferase programme; a novel role for GCN5L1. Biochemical Journal. 2012; 443: 655-61.
Scott I. Regulation of cellular homeostasis by reversible lysine acetylation. Essays in Biochemistry. 2012; 52: 13-22.
Webster BR, Lu Z, Sack MN, Scott I. The role of sirtuins in modulating redox stress. Free Radical Biology and Medicine. 2012; 52: 281-90.
Bao J, Scott I, Lu Z, Pang L, Dimond CC, Gius D, Sack MN. SIRT3 is regulated by nutrient excess and modulates hepatic susceptibility to lipotoxicity. Free Radical Biology and Medicine. 2010; 49: 1230-37.
Lu Z, Scott I, Webster BR, Sack MN. The Emerging Characterization of Lysine Residue Deacetylation on the Modulation of Mitochondrial Function and Cardiovascular Biology. Circulation Research. 2009; 105: 830-41.
Scott I. Degradation of RIG-I following cytomegalovirus infection is independent of apoptosis. Microbes and Infection. 2009; 11: 973-79.
Scott I, Norris KL. The Mitochondrial Antiviral Signaling Protein, MAVS, Is Cleaved During Apoptosis. Biochemical and Biophysical Research Communications. 2008; 375: 101-6.
Sponsored Research/Activities
Title: Regulation of Mitochondrial Function By a Novel Lysine Acetyltransferase
Role: Principal Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: K22 HL116728
Start Year: 2014
End Year: 2017
Title: Regulation of Fuel Utilization by Lysine Acetylation in the Failing Heart
Role: Co-Investigator
Funding Agency: National Heart, Lung, & Blood Institute
Grant Number: R01 HL132917
Start Year: 2017
End Year: 2021
Title: Regulation of Hepatic Mitochondrial Homeostasis and Fuel Metabolism by Acetylation
Role: Co-Investigator
Funding Agency: American Diabetes Association
Grant Number: RES
Start Year: 2017
End Year: 2019
Notable Achievements
Special Act Award, National Institutes of Health, 2014
Young Investigator Award, Society for Redox Biology and Medicine, 2012
Fellows Award for Research Excellence, National Institutes of Health, 2010