TY - JOUR
T1 - Metabolism leaves its mark on the powerhouse
T2 - Recent progress in post-translational modifications of lysine in mitochondria
AU - Papanicolaou, Kyriakos
AU - O'Rourke, Brian
AU - Foster, D. Brian
PY - 2014
Y1 - 2014
N2 - Lysine modifications have been studied extensively in the nucleus, where they play pivotal roles in gene regulation and constitute one of the pillars of epigenetics. In the cytoplasm, they are critical to proteostasis. However, in the last decade we have also witnessed the emergence of mitochondria as a prime locus for post-translational modification of lysine thanks, in large measure, to evolving proteomic techniques. Here, we review recent work on evolving set of post-translational modifications that arise from the direct reaction of lysine residues with energized metabolic thioester-coenzyme A intermediates, including acetylation, succinylation, malonylation and glutarylation. We highlight the evolutionary conservation, kinetics, stoichiometry and cross-talk between members of this emerging family of PTMs. We examine the impact on target protein function and regulation by mitochondrial sirtuins. Finally, we spotlight work in the heart and cardiac mitochondria, and consider the roles acetylation and other newly-found modifications may play in heart disease.
AB - Lysine modifications have been studied extensively in the nucleus, where they play pivotal roles in gene regulation and constitute one of the pillars of epigenetics. In the cytoplasm, they are critical to proteostasis. However, in the last decade we have also witnessed the emergence of mitochondria as a prime locus for post-translational modification of lysine thanks, in large measure, to evolving proteomic techniques. Here, we review recent work on evolving set of post-translational modifications that arise from the direct reaction of lysine residues with energized metabolic thioester-coenzyme A intermediates, including acetylation, succinylation, malonylation and glutarylation. We highlight the evolutionary conservation, kinetics, stoichiometry and cross-talk between members of this emerging family of PTMs. We examine the impact on target protein function and regulation by mitochondrial sirtuins. Finally, we spotlight work in the heart and cardiac mitochondria, and consider the roles acetylation and other newly-found modifications may play in heart disease.
KW - Acetylation
KW - Butyrylation
KW - Crotonylation
KW - Glutarylation
KW - Heart
KW - Malonylation
KW - Propionylation
KW - Sirt3
KW - Sirt5
KW - Sirtuin
KW - Succinylation
UR - http://www.scopus.com/inward/record.url?scp=84907327882&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907327882&partnerID=8YFLogxK
U2 - 10.3389/fphys.2014.00301
DO - 10.3389/fphys.2014.00301
M3 - Review article
C2 - 25228883
AN - SCOPUS:84907327882
SN - 1664-042X
VL - 5 JUL
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - Article 301
ER -