title: Understanding the acetylome: translating targeted proteomics into meaningful physiology.
abstract: It is well established that exercise elicits a finely tuned adaptive response in skeletal muscle, with contraction frequency, duration, and recovery shaping skeletal muscle plasticity. Given the power of physical activity to regulate metabolic health, numerous research groups have focused on the molecular mechanisms that sense, interpret, and translate this contractile signal into postexercise adaptation. While our current understanding is that contraction-sensitive allosteric factors (e.g., Ca(2+), AMP, NAD(+), and acetyl-CoA) initiate signaling changes, how the muscle translates changes in these factors into the appropriate adaptive response remains poorly understood. During the past decade, systems biology approaches, utilizing "omics" screening techniques, have allowed researchers to define global processes of regulation with incredible sensitivity and specificity. As a result, physiologists are now able to study substrate flux with stable isotope tracers in combination with metabolomic approaches and to coordinate these functional changes with proteomic and transcriptomic analysis. In this review, we highlight lysine acetylation as an important posttranslational modification in skeletal muscle. We discuss the evolution of acetylation research and detail how large proteomic screens in diverse metabolic systems have led to the current hypothesis that acetylation may be a fundamental mechanism to fine-tune metabolic adaptation in skeletal muscle.
authors.affiliation: School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom; and a.philp@bham.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Philp
authors.affiliation: School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rowland
authors.affiliation: School of Sport, Exercise, and Rehabilitation Sciences, University of Birmingham, Birmingham, United Kingdom; and.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Perez-Schindler
authors.affiliation: Department of Orthopaedic Surgery, University of California, San Diego, La Jolla, California.
authors.forename: Simon
authors.initials: S
authors.lastname: Schenk
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D051548:Histone Acetyltransferases / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology; D011499:Protein Processing, Post-Translational; D040901:Proteomics
chemical_list: D024101:Mitochondrial Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D008239:Lysine
keywords: adaptation; exercise; metabolism; mitochondria; muscle