Metabolomics-assisted proteomics identifies succinylation and SIRT5 as important regulators of cardiac function

Proceedings of the National Academy of Sciences of the United States of America

Volumn 113, Issue 16, 2016, Pages 4320-4325

  Sadhukhan, Sushabhan ^a   Liu, Xiaojing ^b,c   Ryu, Dongryeol ^d   Nelson, Ornella D ^a   Stupinski, John A ^a   Li, Zhi ^a   Chen, Wei ^e   Zhang, Sheng ^e   Weiss, Robert S ^a   Locasale, Jason W ^b,c   Auwerx, Johan ^d   Lin, Hening ^a  

^a Department of Obstetrics Gynecology   (United States)

^b DUKE CANCER INSTITUTE   (United States)

^c DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d EPFL   (Switzerland)

^e Cornell University   (United States)

Author keywords

Desuccinylation; Fatty acid metabolism; Hypertrophic cardiomyopathy; Lysine succinylation; Sirtuin

Indexed keywords

ADENOSINE TRIPHOSPHATE; LONG CHAIN FATTY ACID; LYSINE; MITOCHONDRIAL PROTEIN; SIRTUIN 5; SUCCINYL COENZYME A; ACYL COENZYME A; FATTY ACID; SIRT5 PROTEIN, MOUSE; SIRTUIN;

AGING; ANIMAL TISSUE; ARTICLE; CARDIOMYOPATHY; CHEMICAL MODIFICATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DOWN REGULATION; FATTY ACID METABOLISM; FATTY ACID OXIDATION; HEART EJECTION FRACTION; HEART FUNCTION; HEART MUSCLE METABOLISM; HEART VENTRICLE HYPERTROPHY; HEART WEIGHT; HYPERTROPHIC CARDIOMYOPATHY; METABOLOMICS; MOUSE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; PROTEOMICS; SUCCINYLATION; WESTERN BLOTTING; ACYLATION; ANIMAL; CARDIAC MUSCLE; CARDIOMEGALY; GENETICS; KNOCKOUT MOUSE; METABOLISM; OXIDATION REDUCTION REACTION; PATHOLOGY; PROCEDURES; PROTEIN PROCESSING;

ACYL COENZYME A; ACYLATION; ANIMALS; CARDIOMEGALY; FATTY ACIDS; METABOLOMICS; MICE; MICE, KNOCKOUT; MYOCARDIUM; OXIDATION-REDUCTION; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEOMICS; SIRTUINS;

EID: 84964374813     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1519858113     Document Type: Article

References (52)

1. Du J, et al. (2011) Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase. Science 334(6057):806-809.
2. Lin H, Su X, He B (2012) Protein lysine acylation and cysteine succination by intermediates of energy metabolism. ACS Chem Biol 7(6):947-960.
3. Tan M, et al. (2011) Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 146(6):1016-1028.
4. Zhang Z, et al. (2011) Identification of lysine succinylation as a new post-translational modification. Nat Chem Biol 7(1):58-63.
5. Chen Y, et al. (2007) Lysine propionylation and butyrylation are novel post-translational modifications in histones. Mol Cell Proteomics 6(5):812-819.
6. Dai L, et al. (2014) Lysine 2-hydroxyisobutyrylation is a widely distributed active histone mark. Nat Chem Biol 10(5):365-370.
7. Jiang H, et al. (2013) SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine. Nature 496(7443):110-113.
8. Tan M, et al. (2014) Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab 19(4):605-617.
9. Zhu AY, et al. (2012) Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine. ACS Chem Biol 7(1):155-159.
10. Yang X-J, Seto E (2008) Lysine acetylation: Codified crosstalk with other posttranslational modifications. Mol Cell 31(4):449-461.
11. Zhao S, et al. (2010) Regulation of cellular metabolism by protein lysine acetylation. Science 327(5968):1000-1004.
12. Pirinen E, Lo Sasso G, Auwerx J (2012) Mitochondrial sirtuins and metabolic homeostasis. Best Pract Res Clin Endocrinol Metab 26(6):759-770.
13. Zhong L, Mostoslavsky R (2011) Fine tuning our cellular factories: Sirtuins in mitochondrial biology. Cell Metab 13(6):621-626.
14. Rauh D, et al. (2013) An acetylome peptide microarray reveals specificities and deacetylation substrates for all human sirtuin isoforms. Nat Commun 4:2327.
15. Lin Z-F, et al. (2013) SIRT5 desuccinylates and activates SOD1 to eliminate ROS. Biochem Biophys Res Commun 441(1):191-195.
16. Park J, et al. (2013) SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol Cell 50(6):919-930.
17. Peng C, et al. (2011) The first identification of lysine malonylation substrates and its regulatory enzyme. Mol Cell Proteomics 10(12):012658.
18. Rardin MJ, et al. (2013) SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. Cell Metab 18(6):920-933.
19. Weinert BT, et al. (2013) Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. Cell Reports 4(4):842-851.
20. Lombard DB, et al. (2007) Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol 27(24):8807-8814.
21. Yu J, et al. (2013) Metabolic characterization of a Sirt5 deficient mouse model. Sci Rep 3:2806.
22. Nakagawa T, Lomb DJ, Haigis MC, Guarente L (2009) SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 137(3):560-570.
23. Boersema PJ, Raijmakers R, Lemeer S, Mohammed S, Heck A J R (2009) Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics. Nat Protoc 4(4):484-494.
24. Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44-57.
25. Huang W, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37(1):1-13.
26. Uchida Y, Izai K, Orii T, Hashimoto T (1992) Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. II. Purification and properties of enoyl-coenzyme A (CoA) hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein. J Biol Chem 267(2):1034-1041.
27. Fong JC, Schulz H (1981) Short-chain and long-chain enoyl-CoA hydratases from pig heart muscle. Methods Enzymol 71(Pt C):390-398.
28. Venkatesan R, Wierenga RK (2013) Structure of mycobacterial β-oxidation trifunctional enzyme reveals its altered assembly and putative substrate channeling pathway. ACS Chem Biol 8(5):1063-1073.
29. Ingwall JS (2001) ATP and the Heart (Kluwer, Boston).
30. Katz AM (1993) Metabolism of the failing heart. Cardioscience 4(4):199-203.
31. Imai S, Armstrong CM, Kaeberlein M, Guarente L (2000) Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403(6771):795-800.
32. Nishida Y, et al. (2015) SIRT5 regulates both cytosolic and mitochondrial protein malonylation with glycolysis as a major target. Mol Cell 59(2):321-332.
33. Herrmann G, Decherd J G M (1939) The chemical nature of heart failure. Ann Intern Med 12(8):1233-1244.
34. Antozzi C, Zeviani M (1997) Cardiomyopathies in disorders of oxidative metabolism. Cardiovasc Res 35(2):184-199.
35. Guertl B, Noehammer C, Hoefler G (2000) Metabolic cardiomyopathies. Int J Exp Pathol 81(6):349-372.
36. Neubauer S (2007) The failing heart-an engine out of fuel. N Engl J Med 356(11):1140-1151.
37. den Boer MEJ, et al. (2003) Mitochondrial trifunctional protein deficiency: A severe fatty acid oxidation disorder with cardiac and neurologic involvement. J Pediatr 142(6):684-689.
38. Brackett JC, et al. (1995) Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency. J Clin Invest 95(5):2076-2082.
39. Boylston JA, et al. (2015) Characterization of the cardiac succinylome and its role in ischemia-reperfusion injury. J Mol Cell Cardiol 88:73-81.
40. Gibson GE, et al. (2015) Alpha-ketoglutarate dehydrogenase complex-dependent succinylation of proteins in neurons and neuronal cell lines. J Neurochem 134(1):86-96.
41. Wagner GR, Payne RM (2013) Widespread and enzyme-independent Ne-acetylation and Ne-succinylation of proteins in the chemical conditions of the mitochondrial matrix. J Biol Chem 288(40):29036-29045.
42. Dils R, Carey EM (1975) Fatty acid synthase from rabbit mammary gland. Methods Enzymol 35:74-83.
43. Yang Y, et al. (2011) Evaluation of different multidimensional LC-MS/MS pipelines for isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of potato tubers in response to cold storage. J Proteome Res 10(10):4647-4660.
44. Srere PA, Kosicki GW (1961) The purification of citrate-condensing enzyme. J Biol Chem 236(10):2557-2559.
45. Ryu D, et al. (2014) A SIRT7-dependent acetylation switch of GABPβ1 controls mitochondrial function. Cell Metab 20(5):856-869.
46. Madonna R, Wu H, Shelat H, Geng YJ (2013) CD1d-associated expression of NF-kB and cardiac dysfunction in diabetic and obese mice. Int J Immunopathol Pharmacol 26(1):59-73.
47. Longhurst JC, Kelly AR, Gonyea WJ, Mitchell JH (1980) Cardiovascular responses to static exercise in distance runners and weight lifters. J Appl Physiol 49(4):676-683.
48. Kessler KM (1979) Ejection fraction derived by M-mode echocardiography: A table and comments. Cathet Cardiovasc Diagn 5(3):295-299.
49. Gariani K, et al. (2015) Eliciting the mitochondrial unfolded protein response via NAD repletion reverses fatty liver disease. Hepatology, 10.1002/hep. 28245.
50. Perino A, et al. (2014) TGR5 reduces macrophage migration through mTOR-induced C/EBPβ differential translation. J Clin Invest 124(12):5424-5436.
51. Boyle KE, Zheng D, Anderson EJ, Neufer PD, Houmard JA (2012) Mitochondrial lipid oxidation is impaired in cultured myotubes from obese humans. Int J Obes 36(8):1025-1031.
52. Lemieux H, Semsroth S, Antretter H, Höfer D, Gnaiger E (2011) Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart. Int J Biochem Cell Biol 43(12):1729-1738.