Protein Post-Translational Modifications Based on Proteomics: A Potential Regulatory Role in Animal Science.

Genomic studies in animal breeding have provided a wide range of references; however, it is important to note that genes and mRNA alone do not fully capture the complexity of living organisms. Protein post-translational modification, which involves covalent modifications regulated by genetic and environmental factors, serves as a fundamental epigenetic mechanism that modulates protein structure, activity, and function. In this review, we comprehensively summarize various phosphorylation and acylation modifications on metabolic enzymes relevant to energy metabolism in animals, including acetylation, succinylation, crotonylation, β-hydroxybutylation, acetoacetylation, and lactylation. It is worth noting that research on animal energy metabolism and modification regulation lags behind the demands for growth and development in animal breeding compared to human studies. Therefore, this review provides a novel research perspective by exploring unreported types of modifications in livestock based on relevant findings from human or animal models.

[1]  Jiaqi Xu,et al.  α-myosin heavy chain lactylation maintains sarcomeric structure and function and alleviates the development of heart failure , 2023, Cell Research.

[2]  Q. Ni,et al.  Cryopreservation Induces Acetylation of Metabolism-Related Proteins in Boar Sperm , 2023, International journal of molecular sciences.

[3]  Yingming Zhao,et al.  Identification of Histone Lysine Acetoacetylation as a Dynamic Post‐Translational Modification Regulated by HBO1 , 2023, Advanced science.

[4]  Zi Shi,et al.  Trash to treasure: lactate and protein lactylation in maize root impacts response to drought , 2023, Science China Life Sciences.

[5]  Hui Peng,et al.  Qualitative lysine crotonylation and 2-hydroxyisobutyrylation analysis in the ovarian tissue proteome of piglets , 2023, Frontiers in Cell and Developmental Biology.

[6]  Junlin He,et al.  Maternal exposure to dibutyl phthalate regulates MSH6 crotonylation to impair homologous recombination in fetal oocytes. , 2023, Journal of hazardous materials.

[7]  Yuan Yuan,et al.  The emerging role of lysine succinylation in ovarian aging , 2023, Reproductive Biology and Endocrinology.

[8]  Xiaohu Zheng,et al.  SIRT3‐dependent delactylation of cyclin E2 prevents hepatocellular carcinoma growth , 2023, EMBO reports.

[9]  S. Qiu,et al.  Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma , 2023, Nature Metabolism.

[10]  Ferdinand von Meyenn,et al.  H3K18 lactylation marks tissue-specific active enhancers , 2022, Genome Biology.

[11]  M. Klemsz,et al.  Inhibition of MEK signaling prevents SARS‐CoV2‐induced lung damage and improves the survival of infected mice , 2022, Journal of medical virology.

[12]  Duan Tingting,et al.  Transcriptome-based analysis of early post-mortem formation of pale, soft, and exudative (PSE) pork. , 2022, Meat science.

[13]  L. Pirola,et al.  Ketogenic diet administration to mice after a high-fat-diet regimen promotes weight loss, glycemic normalization and induces adaptations of ketogenic pathways in liver and kidney , 2022, Molecular metabolism.

[14]  C. Olsen,et al.  Chiral Posttranslational Modification to Lysine ε-Amino Groups. , 2022, Accounts of chemical research.

[15]  J Zhang,et al.  Positive feedback regulation of microglial glucose metabolism by histone H4 lysine 12 lactylation in Alzheimer's disease. , 2022, Cell metabolism.

[16]  J. Bayascas,et al.  Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice , 2022, Cell death & disease.

[17]  Xuelian Ren,et al.  Quantitative Proteomics Analysis Expands the Roles of Lysine β-Hydroxybutyrylation Pathway in Response to Environmental β-Hydroxybutyrate , 2022, Oxidative medicine and cellular longevity.

[18]  A. Akhtar,et al.  Modulation of cellular processes by histone and non-histone protein acetylation , 2022, Nature Reviews Molecular Cell Biology.

[19]  Peijun Wang,et al.  Hypoxic in vitro culture reduces histone lactylation and impairs pre-implantation embryonic development in mice , 2021, Epigenetics & chromatin.

[20]  M. Hirata,et al.  Aberrant levels of DNA methylation and H3K9 acetylation in the testicular cells of crossbred cattle-yak showing infertility. , 2021, Reproduction in domestic animals = Zuchthygiene.

[21]  Guohong Chen,et al.  Comparative phosphoproteomic provides insights into meat quality differences between slow- and fast-growing broilers. , 2021, Food chemistry.

[22]  Graziano Martello,et al.  Y705 and S727 are required for the mitochondrial import and transcriptional activities of STAT3, and for regulation of stem cell proliferation , 2021, Development.

[23]  David L. Williams,et al.  Lactate promotes macrophage HMGB1 lactylation, acetylation, and exosomal release in polymicrobial sepsis , 2021, Cell death and differentiation.

[24]  Mario Leutert,et al.  Decoding Post-Translational Modification Crosstalk With Proteomics , 2021, Molecular & cellular proteomics : MCP.

[25]  Qingrui Zhuan,et al.  Nampt affects mitochondrial function in aged oocytes by mediating the downstream effector FoxO3a , 2021, Journal of cellular physiology.

[26]  Xiaoxi Meng,et al.  Comprehensive Analysis of Lysine Lactylation in Rice (Oryza sativa) Grains. , 2021, Journal of agricultural and food chemistry.

[27]  R. Schneider,et al.  Histone acylations and chromatin dynamics: concepts, challenges, and links to metabolism , 2021, EMBO reports.

[28]  Jun Shi,et al.  Lactylation, a Novel Metabolic Reprogramming Code: Current Status and Prospects , 2021, Frontiers in Immunology.

[29]  Yingming Zhao,et al.  Class I histone deacetylases (HDAC1–3) are histone lysine delactylases , 2021, bioRxiv.

[30]  Xianqun Fan,et al.  Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma , 2021, Genome biology.

[31]  H. Shoji,et al.  Protein lactylation induced by neural excitation , 2021, bioRxiv.

[32]  R. Roeder,et al.  The regulatory enzymes and protein substrates for the lysine β-hydroxybutyrylation pathway , 2021, Science Advances.

[33]  J. Bae,et al.  Effects of exercise‐induced beta‐hydroxybutyrate on muscle function and cognitive function , 2021, Physiological reports.

[34]  J. Michaelis,et al.  Succinylation of H3K122 destabilizes nucleosomes and enhances transcription , 2021, EMBO reports.

[35]  Yingming Zhao,et al.  Ketogenesis impact on liver metabolism revealed by proteomics of lysine β-hydroxybutyrylation , 2021, bioRxiv.

[36]  Xiaoling Li,et al.  Histone crotonylation promotes mesoendodermal commitment of human embryonic stem cells. , 2021, Cell stem cell.

[37]  Jeffrey R. Whiteaker,et al.  Proteogenomic Landscape of Breast Cancer Tumorigenesis and Targeted Therapy , 2020, Cell.

[38]  D. Xia,et al.  Lysine acetylation participates in boar spermatozoa motility and acrosome status regulation under different glucose conditions. , 2020, Theriogenology.

[39]  Xu Yanli,et al.  Proteomics analysis as an approach to understand the formation of pale, soft, and exudative (PSE) pork. , 2020, Meat science.

[40]  Qingrui Zhuan,et al.  Procyanidin B2 Improves Oocyte Maturation and Subsequent Development in Type 1 Diabetic Mice by Promoting Mitochondrial Function , 2020, Reproductive Sciences.

[41]  Xiangmei Zhou,et al.  Global quantitative phosphoproteome reveals phosphorylation network of bovine lung tissue altered by Mycobacterium bovis. , 2020, Microbial pathogenesis.

[42]  M. Potente,et al.  Endothelial Cells Don't Waste: Endothelial-Derived Lactate Boosts Muscle Regeneration. , 2020, Developmental cell.

[43]  Junming Xu,et al.  Integrative Proteomic Characterization of Human Lung Adenocarcinoma , 2020, Cell.

[44]  J. Rabinowitz,et al.  Lactate: the ugly duckling of energy metabolism , 2020, Nature Metabolism.

[45]  Chunbao Li,et al.  Acetylation and Phosphorylation of Proteins Affect Energy Metabolism and Pork Quality. , 2020, Journal of agricultural and food chemistry.

[46]  P. Carmeliet,et al.  Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization , 2020, Cell metabolism.

[47]  Lin He,et al.  Global crotonylome reveals CDYL-regulated RPA1 crotonylation in homologous recombination–mediated DNA repair , 2020, Science Advances.

[48]  Devin K. Schweppe,et al.  A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging , 2020, Cell.

[49]  Xin Li,et al.  Effects of temperature on protein phosphorylation in postmortem muscle. , 2020, Journal of the science of food and agriculture.

[50]  M. Sharafi,et al.  Cryopreservation of rooster semen: Evidence for the epigenetic modifications of thawed sperm. , 2020, Theriogenology.

[51]  M. Won,et al.  DDIAS promotes STAT3 activation by preventing STAT3 recruitment to PTPRM in lung cancer cells , 2020, Oncogenesis.

[52]  Xiaoying Ye,et al.  Functional Oocytes Derived from Granulosa Cells. , 2019, Cell reports.

[53]  Q. Shen,et al.  Proteomic analysis reveals that lysine acetylation mediates the effect of antemortem stress on postmortem meat quality development. , 2019, Food chemistry.

[54]  B. Ren,et al.  Metabolic regulation of gene expression by histone lactylation , 2019, Nature.

[55]  Minjia Tan,et al.  Global proteomic analysis of lysine succinylation in zebrafish (Danio rerio). , 2019, Journal of proteome research.

[56]  Q. Shen,et al.  Acetylome profiling reveals extensive involvement of lysine acetylation in the conversion of muscle to meat. , 2019, Journal of proteomics.

[57]  J. Workman,et al.  Histone lysine de-β-hydroxybutyrylation by SIRT3 , 2019, Cell Research.

[58]  Haitao Li,et al.  Molecular basis for hierarchical histone de-β-hydroxybutyrylation by SIRT3 , 2019, Cell Discovery.

[59]  Wei Shan,et al.  Ketone Bodies in Neurological Diseases: Focus on Neuroprotection and Underlying Mechanisms , 2019, Front. Neurol..

[60]  Oliver M. Bernhardt,et al.  Rapid and site-specific deep phosphoproteome profiling by data-independent acquisition without the need for spectral libraries , 2019, Nature Communications.

[61]  Mingwei Liu,et al.  Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma , 2019, Nature.

[62]  Juan Antonio Vizcaíno,et al.  The functional landscape of the human phosphoproteome , 2019, Nature Biotechnology.

[63]  Haitao Li,et al.  Beyond histone acetylation-writing and erasing histone acylations. , 2018, Current opinion in structural biology.

[64]  Chunaram Choudhary,et al.  Functions and mechanisms of non-histone protein acetylation , 2018, Nature Reviews Molecular Cell Biology.

[65]  M. Blades,et al.  Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo , 2018, Scientific Reports.

[66]  M. Li,et al.  Quantitative phosphoproteomic analysis among muscles of different color stability using tandem mass tag labeling. , 2018, Food chemistry.

[67]  C. Craik,et al.  Global substrate specificity profiling of post‐translational modifying enzymes , 2018, Protein science : a publication of the Protein Society.

[68]  Sangkyu Lee,et al.  First profiling of lysine crotonylation of myofilament proteins and ribosomal proteins in zebrafish embryos , 2018, Scientific Reports.

[69]  Chunchun Han,et al.  Transcriptome analysis revealed the possible regulatory pathways initiating female geese broodiness within the hypothalamic-pituitary-gonadal axis , 2018, PloS one.

[70]  M. Veldhoen,et al.  Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases , 2018, Nature Communications.

[71]  Jie He,et al.  KAT2A coupled with the α-KGDH complex acts as a histone H3 succinyltransferase , 2017, Nature.

[72]  Lin He,et al.  Chromodomain Protein CDYL Acts as a Crotonyl-CoA Hydratase to Regulate Histone Crotonylation and Spermatogenesis. , 2017, Molecular cell.

[73]  Tieliu Shi,et al.  MOF as an evolutionarily conserved histone crotonyltransferase and transcriptional activation by histone acetyltransferase-deficient and crotonyltransferase-competent CBP/p300 , 2017, Cell Discovery.

[74]  Tieliu Shi,et al.  Class I histone deacetylases are major histone decrotonylases: evidence for critical and broad function of histone crotonylation in transcription , 2017, Cell Research.

[75]  Weizhi Xu,et al.  Global profiling of crotonylation on non-histone proteins , 2017, Cell Research.

[76]  Q. Shen,et al.  Effects of protein phosphorylation on color stability of ground meat. , 2017, Food chemistry.

[77]  F. Xue,et al.  Exploration of candidate biomarkers for human psoriasis based on gas chromatography‐mass spectrometry serum metabolomics , 2017, The British journal of dermatology.

[78]  P. Puchalska,et al.  Multi-dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics. , 2017, Cell metabolism.

[79]  Tor W. Jensen,et al.  Impact of β-hydroxy β-methylbutyrate (HMB) on age-related functional deficits in mice , 2017, Experimental Gerontology.

[80]  Di Zhang,et al.  Metabolic regulation of gene expression through histone acylations , 2016, Nature Reviews Molecular Cell Biology.

[81]  C. Allis,et al.  Selective recognition of histone crotonylation by double PHD fingers of MOZ and DPF2. , 2016, Nature chemical biology.

[82]  T. Arnesen,et al.  The world of protein acetylation. , 2016, Biochimica et biophysica acta.

[83]  Ming-Ming Zhou,et al.  Structural Insights into Histone Crotonyl-Lysine Recognition by the AF9 YEATS Domain. , 2016, Structure.

[84]  Lin He,et al.  SIRT7 is a histone desuccinylase that functionally links to chromatin compaction and genome stability , 2016, Nature Communications.

[85]  C. Qian,et al.  Post-Translational Modification Control of Innate Immunity. , 2016, Immunity.

[86]  Q. Shen,et al.  Antemortem stress regulates protein acetylation and glycolysis in postmortem muscle. , 2016, Food chemistry.

[87]  C. Allis,et al.  YEATS2 is a selective histone crotonylation reader , 2016, Cell Research.

[88]  Haipeng Guan,et al.  Molecular Coupling of Histone Crotonylation and Active Transcription by AF9 YEATS Domain. , 2016, Molecular cell.

[89]  Hongyu Zhao,et al.  Metabolic Regulation of Gene Expression by Histone Lysine β-Hydroxybutyrylation. , 2016, Molecular cell.

[90]  Q. Shen,et al.  Phosphorylation of myofibrillar proteins in post-mortem ovine muscle with different tenderness. , 2016, Journal of the science of food and agriculture.

[91]  K. Baumann Post-translational modifications: Crotonylation versus acetylation , 2015, Nature Reviews Molecular Cell Biology.

[92]  C. Allis,et al.  Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation. , 2015, Molecular cell.

[93]  B. Garcia,et al.  Quantitative proteomic analysis of histone modifications. , 2015, Chemical reviews.

[94]  M. Mann,et al.  Ultradeep human phosphoproteome reveals a distinct regulatory nature of Tyr and Ser/Thr-based signaling. , 2014, Cell reports.

[95]  F. Fang,et al.  Dynamic changes of histone H3 lysine 27 acetylation in pre-implantational pig embryos derived from somatic cell nuclear transfer. , 2014, Animal reproduction science.

[96]  B. Kemp,et al.  Compensatory regulation of HDAC5 in muscle maintains metabolic adaptive responses and metabolism in response to energetic stress , 2014, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[97]  Matthew J. Rardin,et al.  SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. , 2013, Cell metabolism.

[98]  A. D’Alessandro,et al.  Foodomics to investigate meat tenderness , 2013 .

[99]  Sebastian A. Wagner,et al.  Lysine succinylation is a frequently occurring modification in prokaryotes and eukaryotes and extensively overlaps with acetylation. , 2013, Cell reports.

[100]  Yingming Zhao,et al.  SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. , 2013, Molecular cell.

[101]  Eric Verdin,et al.  Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor , 2013, Science.

[102]  C. Olsen,et al.  Profiling of substrates for zinc-dependent lysine deacylase enzymes: HDAC3 exhibits decrotonylase activity in vitro. , 2012, Angewandte Chemie.

[103]  A. D’Alessandro,et al.  Love me tender: an Omics window on the bovine meat tenderness network. , 2012, Journal of proteomics.

[104]  A. Mozzarelli,et al.  "Muscle to meat" molecular events and technological transformations: the proteomics insight. , 2012, Journal of proteomics.

[105]  E. Porcu,et al.  Vitrification of pig oocytes induces changes in histone H4 acetylation and histone H3 lysine 9 methylation (H3K9) , 2012, Veterinary Research Communications.

[106]  A. Hartman,et al.  Ketone bodies in epilepsy , 2012, Journal of neurochemistry.

[107]  Johan Auwerx,et al.  Sirt5 Is a NAD-Dependent Protein Lysine Demalonylase and Desuccinylase , 2011, Science.

[108]  M. Larsen,et al.  Gel‐based phosphoproteomics analysis of sarcoplasmic proteins in postmortem porcine muscle with pH decline rate and time differences , 2011, Proteomics.

[109]  Zhike Lu,et al.  Identification of 67 Histone Marks and Histone Lysine Crotonylation as a New Type of Histone Modification , 2011, Cell.

[110]  D. Blum,et al.  D-β-Hydroxybutyrate Is Protective in Mouse Models of Huntington's Disease , 2011, PloS one.

[111]  Kun-Liang Guan,et al.  Regulation of intermediary metabolism by protein acetylation. , 2011, Trends in biochemical sciences.

[112]  Edward L. Huttlin,et al.  A Tissue-Specific Atlas of Mouse Protein Phosphorylation and Expression , 2010, Cell.

[113]  Guo-Ping Zhao,et al.  Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux , 2010, Science.

[114]  Junjie Hou,et al.  Phosphoproteome analysis of rat L6 myotubes using reversed-phase C18 prefractionation and titanium dioxide enrichment. , 2010, Journal of proteome research.

[115]  E. Sato,et al.  Acetylation level of histone H3 in early embryonic stages affects subsequent development of miniature pig somatic cell nuclear transfer embryos. , 2009, The Journal of reproduction and development.

[116]  C. Flynn,et al.  In vivo phosphoproteome of human skeletal muscle revealed by phosphopeptide enrichment and HPLC-ESI-MS/MS. , 2009, Journal of proteome research.

[117]  Yingming Zhao,et al.  Modification‐specific proteomics: Strategies for characterization of post‐translational modifications using enrichment techniques , 2009, Proteomics.

[118]  M. Mann,et al.  Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions , 2009, Science.

[119]  P. Puigserver,et al.  AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity , 2009, Nature.

[120]  Yingming Zhao,et al.  PTMap—A sequence alignment software for unrestricted, accurate, and full-spectrum identification of post-translational modification sites , 2009, Proceedings of the National Academy of Sciences.

[121]  Lisa Staunton,et al.  Phosphoproteomic analysis of aged skeletal muscle. , 2008, International journal of molecular medicine.

[122]  D E Gerrard,et al.  Mechanisms controlling pork quality development: The biochemistry controlling postmortem energy metabolism. , 2007, Meat science.

[123]  M. Grunstein,et al.  Functions of site-specific histone acetylation and deacetylation. , 2007, Annual review of biochemistry.

[124]  N. Grishin,et al.  Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. , 2006, Molecular cell.

[125]  George F Cahill,et al.  Fuel metabolism in starvation. , 2006, Annual review of nutrition.

[126]  Sylvie Garneau-Tsodikova,et al.  Protein posttranslational modifications: the chemistry of proteome diversifications. , 2005, Angewandte Chemie.

[127]  Timothy Cardozo,et al.  The SCF ubiquitin ligase: insights into a molecular machine , 2004, Nature Reviews Molecular Cell Biology.

[128]  M. Díaz-Ricart,et al.  Differences and similarities in tyrosine phosphorylation of proteins in platelets from human and pig species , 2003, Journal of thrombosis and haemostasis : JTH.

[129]  S. Elledge,et al.  Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex , 2002, Nature.

[130]  A. Giordano,et al.  Acetyltransferase machinery conserved in p300/CBP-family proteins , 2002, Oncogene.

[131]  J. Shabanowitz,et al.  Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae , 2002, Nature Biotechnology.

[132]  K. Clarke,et al.  D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[133]  M. Karin Signal transduction from the cell surface to the nucleus through the phosphorylation of transcription factors. , 1994, Current opinion in cell biology.

[134]  S. Sprang,et al.  Structural changes in glycogen phosphorylase induced by phosphorylation , 1988, Nature.

[135]  J. Porath,et al.  Isolation of phosphoproteins by immobilized metal (Fe3+) affinity chromatography. , 1986, Analytical biochemistry.

[136]  K. Yoshikawa,et al.  Phosphorylation of pig epidermal soluble protein by endogenous cAMP-dependent protein kinase. , 1983, The Journal of investigative dermatology.

[137]  A. Mirsky,et al.  ACETYLATION AND METHYLATION OF HISTONES AND THEIR POSSIBLE ROLE IN THE REGULATION OF RNA SYNTHESIS. , 1964, Proceedings of the National Academy of Sciences of the United States of America.

[138]  Zhihong Zhang,et al.  Identification of lysine succinylation as a new post-translational modification. , 2011, Nature chemical biology.

[139]  S. Cairns Lactic Acid and Exercise Performance , 2006, Sports medicine.

[140]  L. Gladden,et al.  Muscle as a consumer of lactate. , 2000, Medicine and science in sports and exercise.

[141]  D. Williamson,et al.  Physiological roles of ketone bodies as substrates and signals in mammalian tissues. , 1980, Physiological reviews.