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Regulation of Mitochondrial Metabolism


Instructor: Matthew Hirschey
Summary: This workshop-style module will examine how post-translational modifications can modulate the structure and function of proteins. Protein phosphorylation, ubiquitination, and acylation will be covered. As a working example, we will focus on protein acetylation, which has been shown to modify the majority of metabolic enzymes in the mitochondria. Students will be exposed to basic mitochondrial biology, including functions and dynamics, and then choose an enzyme to perform a detailed analysis of acetylation sites. Methods for identifying putative acetylation sites and performing basic structural analyses will be discussed. Students will then generate novel predictions as to how acetylation might affect their enzyme of choice. Strategies for assessing these hypotheses will also be covered. Although the focus will be on acetylation of mitochondrial proteins, the skills acquired in this module will be broadly applicable.


1) Mitochondrial protein acetylation regulates metabolism. Anderson, K.A., and M.D. Hirschey, 2012, Essays Biochem. 52, 23–35.
2) Molecular Biology of the Cell, Alberts et al., Ch. 14: pp. 813-840.