Acetylation-Mediated Post-Translational Modification of Pyruvate Dehydrogenase Plays a Critical Role in the Regulation of the Cellular Acetylome During Metabolic Stress
Abstract
1. Introduction
2. Methods
2.1. Cell Culture
2.2. Ischemic Conditions
2.3. Cell Harvesting and Protein Isolation
2.4. Western Blotting
2.5. Protein Digestion, Affinity Purification of Acetylated Proteins, and Mass Spectrometry
3. Bioinformatics Analysis
4. Statistical Data Analysis
5. Results
5.1. Ischemic Condition Significantly Reduces the Cellular Acetylation Level
5.2. Identification of Differentially Acetylated Positions in Proteins
5.3. Sequence Motifs of Lysine Acetylation Sites
5.4. Functional Enrichment Analysis of the Acetylated Proteins
5.5. String Protein Web
6. Discussion
7. Future Perspectives
8. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Protein Names | Acetylated Positions | Protein | Acetylation | |
---|---|---|---|---|
1 | ATP synthase subunit alpha; mitochondrial | 259; 261 | F1LP05 | UP |
2 | 14-3-3 protein zeta/delta | 60; 78; 51; 50 | A0A0G2JV65 | UP |
3 | Hyaluronan-mediated motility receptor | 80 | A0A0G2JXY1 | UP |
4 | Hyaluronan-mediated motility receptor | 83 | A0A0G2JXY1 | UP |
5 | Ro60, Y RNA-binding protein | 489 | D3ZRN5 | DOWN |
6 | CREB-binding protein | 1584 | F1M9G7 | DOWN |
7 | CREB-binding protein | 1587 | F1M9G7 | DOWN |
8 | CREB-binding protein | 1588 | F1M9G7 | DOWN |
9 | Aldose reductase | 263 | P07943 | UP |
10 | 40S ribosomal protein S9 | 155 | P29314 | NC |
11 | 14-3-3 protein theta | 49 | P68255 | UP |
12 | Rab9 effector protein with kelch motifs | 2 | Q4V8F4 | UP |
13 | Galectin-1 | 29 | P11762 | UP |
14 | Hematological and neurological expressed 1 protein | 143 | Q6AXU6 | UP |
15 | Gamma-butyrobetaine dioxygenase | 158 | A0A0G2K461 | UP |
16 | Tropomyosin alpha-1 chain | 260 | A0A0G2K7F7 | UP |
17 | Sperm-associated antigen 17 | 142 | M0R8D9 | DOWN |
18 | Sperm-associated antigen 17 | 147 | M0R8D9 | DOWN |
19 | Calpain-6 | 616 | G3V6M4 | NC |
20 | Myosin, heavy polypeptide 9, nonmuscle | 1352 | G3V6P7 | UP |
21 | Myosin-6; Myosin-7 | 1833; 1831 | G3V885 | UP |
22 | Myosin-6 | 1643 | G3V885 | NC |
23 | Myosin-6; Myosin-7 | 1487; 1485 | G3V885 | UP |
24 | Myosin-6; Myosin-7 | 1501; 1499 | G3V885 | UP |
25 | Myosin-6; Myosin-7 | 1365; 1363 | G3V885 | UP |
26 | Myosin light chain 3 | 38 | P16409 | UP |
27 | Myosin light chain 4 | 123; 123 | P17209 | UP |
28 | Centrosomal protein of 295 kDa | 1478 | A0A0G2K417 | NC |
29 | Outer dense fiber protein 2 | 617 | G3V7X0 | UP |
30 | Outer dense fiber protein 2 | 620 | G3V7X0 | UP |
31 | T-complex protein 1 subunit alpha | 400 | P28480 | UP |
32 | Serine hydroxymethyltransferase | 409 | Q5U3Z7 | UP |
33 | Myosin-10 | 1055 | G3V9Y1 | UP |
34 | Myosin-10 | 1057 | G3V9Y1 | UP |
35 | Myosin regulatory light polypeptide 9 | 7 | B0BMS8 | UP |
36 | Myosin regulatory light polypeptide 9 | 12 | B0BMS8 | UP |
37 | Myosin regulatory light polypeptide 9 | 13 | B0BMS8 | UP |
38 | Myosin light polypeptide 6 | 81 | A0A0G2K6J5 | NC |
39 | Myosin-4; Myosin-6; Myosin-7 | 1330; 1328; 1326 | G3V885 | UP |
40 | Alpha-enolase | 5 | M0R5J4 | UP |
41 | 60S ribosomal protein L19 | 153 | M0RDT4 | UP |
42 | 60S ribosomal protein L19 | 163 | M0RDT4 | UP |
43 | 60S ribosomal protein L29 | 45 | A0A0G2QC62 | UP |
44 | 60S ribosomal protein L30 | 46 | A0A0G2QC62 | UP |
45 | 60S ribosomal protein L31 | 49 | A0A0G2QC62 | UP |
46 | Leucyl-tRNA synthetase | 143 | Q5PPJ6 | DOWN |
47 | Leucyl-tRNA synthetase | 145 | Q5PPJ6 | DOWN |
48 | Leucyl-tRNA synthetase | 146 | Q5PPJ6 | DOWN |
49 | Leucyl-tRNA synthetase | 148 | Q5PPJ6 | DOWN |
50 | Ribosome-binding protein 1 | 772 | F1M853 | UP |
51 | Glutamate dehydrogenase 1, mitochondrial | 480 | P10860 | UP |
52 | Elongation factor 1-gamma | 147 | Q68FR6 | UP |
53 | Angiopoietin-like 3 | 425 | F7FHP0 | DOWN |
54 | Uncharacterized protein | 135 | A0A0G2JT80 | DOWN |
55 | Insulin-like growth factor I | 126 | A0A0G2JX40 | UP |
56 | Insulin-like growth factor I | 127 | A0A0G2JX40 | UP |
57 | Vascular endothelial growth factor A | 327 | A0A0H2UHY5 | DOWN |
58 | Vascular endothelial growth factor A | 330 | A0A0H2UHY5 | DOWN |
59 | Fibroblast growth factor | 52 | Q76LI5 | UP |
60 | Fibroblast growth factor | 60 | Q76LI5 | UP |
61 | Pro-interleukin-16 | 487 | D4A4I9 | NC |
62 | Alpha-crystallin B chain | 103 | P23928 | UP |
63 | RCG48016, isoform CRA_c | 67 | D4AAM1 | UP |
64 | RCG48016, isoform CRA_c | 68 | D4AAM1 | UP |
65 | Palmitoyltransferase | 264 | Q2TGK3 | NC |
66 | Annexin | 370 | Q6IMZ3 | UP |
67 | ADP/ATP translocase 1 | 23 | Q6P9Y4 | UP |
68 | ADP/ATP translocase 1 | 96 | Q6P9Y4 | UP |
69 | Pyruvate dehydrogenase E1 component subunit alpha; mitochondrial | 243 | F7FKI5 | UP |
70 | Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex | 195 | A0A0G2JZH8 | UP |
71 | Voltage-dependent anion-selective channel protein 3 | 63 | A0A0G2JSR0 | UP |
72 | 39S ribosomal protein L3, mitochondrial | 213 | G3V7P3 | DOWN |
73 | Similar to orotein C6orf203 | 149 | M0R7R2 | UP |
74 | Malate dehydrogenase, mitochondrial | 185 | P04636 | UP |
75 | Malate dehydrogenase, mitochondrial | 301 | P04636 | UP |
76 | Malate dehydrogenase, mitochondrial | 157 | P04636 | UP |
77 | Cytochrome c oxidase subunit 4 isoform 1, mitochondrial | 29 | P10888 | UP |
78 | Enoyl-CoA hydratase, mitochondrial | 101 | P14604 | UP |
79 | Succinate dehydrogenase [ubiquinone] iron–sulfur subunit, mitochondrial | 64 | P21913 | NC |
80 | 10 kDa heat shock protein, mitochondrial | 80 | P26772 | UP |
81 | Peptidyl-prolyl cis–trans isomerase F, mitochondrial | 72 | P29117 | UP |
82 | GTP: AMP phosphotransferase AK3, mitochondrial | 34 | Q6P2A5 | UP |
83 | ATP synthase subunit d, mitochondrial | 71 | P31399 | UP |
84 | Cytochrome b-c1 complex subunit 2, mitochondrial | 91 | P32551 | UP |
85 | Mitochondrial ribosomal protein L47 | 146 | Q3B8R7 | UP |
86 | Proton-translocating NAD(P)(+) transhydrogenase | 403 | Q5BJZ3 | UP |
87 | Proton-translocating NAD(P)(+) transhydrogenase | 768 | Q5BJZ3 | UP |
88 | Citrate lyase subunit beta-like protein, mitochondrial | 55 | Q5I0K3 | UP |
89 | NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 | 40 | Q63362 | UP |
90 | Trifunctional enzyme subunit alpha, mitochondrial | 60 | Q64428 | UP |
91 | Trifunctional enzyme subunit alpha, mitochondrial | 46 | Q64428 | UP |
92 | Succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial | 242 | Q920L2 | UP |
93 | Aconitate hydratase, mitochondrial | 50 | Q9ER34 | UP |
94 | Pyruvate dehydrogenase E1 component subunit beta, mitochondrial | 132 | A0A0G2KAM3 | UP |
95 | Carnitine O-acetyltransferase | 390 | A0A0H2UI21 | UP |
96 | Enoyl-CoA delta isomerase 2, mitochondrial | 90 | Q5XIC0 | NC |
97 | Myosin regulatory light chain 2, ventricular/cardiac muscle isoform | 165 | P08733 | UP |
98 | Myosin regulatory light chain 2, ventricular/cardiac muscle isoform | 62 | P08733 | UP |
99 | Zinc finger protein 326 | 287 | M0R440 | UP |
100 | Histone domain-containing protein | 16 | A0A0G2K7R1 | UP |
101 | Histone domain-containing protein | 17 | A0A0G2K7R1 | UP |
102 | Histone domain-containing protein | 21 | A0A0G2K7R1 | DOWN |
103 | Histone domain-containing protein | 24 | A0A0G2K7R1 | UP |
104 | Histone domain-containing protein | 13 | A0A0G2K7R1 | NC |
105 | Histone domain-containing protein | 12 | A0A0G2K7R1 | NC |
106 | Histone H2A; Histone H2A.Z | 7 | A0A0A0MXW3 | UP |
107 | Histone H2A; Histone H2A.Z | 11 | A0A0A0MXW3 | UP |
108 | RB-binding protein 4, chromatin-remodeling factor | 4 | B5DFB2 | UP |
109 | Remodeling and spacing factor 1 | 1065 | D3ZGQ8 | UP |
110 | Histone H3; Histone H3.1; Histone H3.3 | 80 | M0RBX6 | UP |
111 | Histone H3; Histone H3.1; Histone H3.3 | 19 | M0RBX6 | UP |
112 | Histone H3; Histone H3.1; Histone H3.3 | 24 | M0RBX6 | UP |
113 | Histone H3; Histone H3.1; Histone H3.3 | 57 | M0RBX6 | UP |
114 | Structural maintenance of chromosomes protein | 105 | F1LQB2 | UP |
115 | Structural maintenance of chromosomes protein | 106 | F1LQB2 | UP |
116 | BARX homeobox 2 | 16 | D4A7E7 | UP |
117 | RNA cytidine acetyltransferase | 8 | D4AEB4 | UP |
118 | Jumonji domain-containing 1C | 345 | F1LMK8 | UP |
119 | H1.3 linker histone, cluster member | 187 | M0R7B4 | UP |
120 | H1.3 linker histone, cluster member | 191 | M0R7B4 | UP |
121 | H1.3 linker histone, cluster member | 193 | M0R7B4 | UP |
122 | Prothymosin alpha | 103 | P06302 | NC |
123 | Heart- and neural crest derivative-expressed protein 1 | 101 | P97832 | UP |
124 | High mobility group protein HMG-I/HMG-Y | 7 | Q8K585 | UP |
125 | Transmembrane protein 176B | 258 | Q925D4 | NC |
126 | Histone H2B | 17 | A0A0G2JXE0 | NC |
127 | Histone H2B | 21 | A0A0G2JXE0 | UP |
128 | Histone H2B | 13 | A0A0G2JXE0 | NC |
129 | Histone H2B | 16 | A0A0G2JXE0 | NC |
130 | Histone H2B; Histone H2B type 1; Histone H2B type 1-A | 109; 109; 109 | M0RBQ5 | UP |
131 | Histone H2B | 12 | A0A0G2JXE0 | |
132 | Histone H2B; Histone H2B type 1 | 16 | M0RBQ5 | NC |
133 | Histone H2B; Histone H2B type 1 | 17 | M0RBQ5 | NC |
134 | Histone H2B; Histone H2B type 1 | 21 | M0RBQ5 | NC |
135 | Histone H2B; Histone H2B type 1 | 24 | M0RBQ5 | NC |
136 | Histone H2B; Histone H2B type 1 | 13 | M0RBQ5 | NC |
137 | Histone H2B | 12 | M0RBQ5 | NC |
138 | Zinc finger protein 821 | 305 | D3ZEI3 | UP |
139 | General transcription factor 3C polypeptide 1 | 1220 | F1LNV7 | NC |
140 | General transcription factor 3C polypeptide 1 | 1222 | F1LNV7 | NC |
141 | Testis-specific Y-encoded protein 1 | 176 | Q9R1M3 | NC |
142 | Heterogeneous nuclear ribonucleoprotein A1 | 3 | Q6P6G9 | UP |
143 | Actin, cytoplasmic 1 | 61; 61; 63 | P60711 | UP |
144 | Histone H4; osteogenic growth peptide | 9 | P62804 | DOWN |
145 | Histone H4; osteogenic growth peptide | 13 | P62804 | DOWN |
146 | Histone H4; osteogenic growth peptide | 17 | P62804 | DOWN |
147 | Histone H4; osteogenic growth peptide | 6 | P62804 | DOWN |
148 | Dihydrolipoyl dehydrogenase, mitochondrial | 334 | Q6P6R2 | UP |
149 | SRY-box containing gene 7 (predicted) | 119 | D3ZTE1 | UP |
150 | SRY-box containing gene 7 (predicted) | 120 | D3ZTE1 | UP |
151 | SRY-box containing gene 7 (predicted) | 123 | D3ZTE1 | UP |
152 | Acyl-coenzyme A amino acid N-acyltransferase 1 | 309 | A0A0G2K2H6 | UP |
153 | Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas | 756 | A0A0G2JWA1 | |
154 | Olfactory receptor | 295 | D3ZL36 | UP |
155 | Olfactory receptor | 302 | D3ZL36 | UP |
156 | Olfactory receptor | 295 | D3ZSI0 | UP |
157 | Olfactory receptor | 296 | D3ZSI0 | UP |
158 | ATP synthase subunit alpha, mitochondrial | 161 | F1LP05 | UP |
159 | Alpha-kinase 2 | 1728 | F1LTG2 | UP |
160 | Aspartate aminotransferase, mitochondrial | 159 | P00507 | UP |
161 | Aspartate aminotransferase, mitochondrial | 296 | P00507 | UP |
162 | N-alpha-acetyltransferase 50-like | 33 | M0RBI3 | UP |
163 | 60S ribosomal protein L14 | 162 | F1LSW7 | UP |
164 | 60S ribosomal protein L15 | 163 | F1LSW7 | UP |
165 | Ryanodine receptor 3 | 4351 | F1LPJ2 | UP |
166 | Ryanodine receptor 4 | 4358 | F1LPJ2 | UP |
167 | SH2 domain-containing 3C | 45 | B0BN10 | UP |
168 | Leucine-rich repeat-containing 69 | 14 | D3Z998 | DOWN |
169 | Leucine-rich repeat-containing 70 | 17 | D3Z998 | DOWN |
170 | Leucine-rich repeat-containing 71 | 24 | D3Z998 | DOWN |
171 | Ligand-dependent nuclear receptor-interacting factor 1 | 90 | B0BNF2 | NC |
172 | Ligand-dependent nuclear receptor-interacting factor 1 | 91 | B0BNF2 | NC |
173 | Peptidyl-prolyl cis–trans isomerase A | 79 | A0A0G2K1P0 | UP |
174 | Peptidyl-prolyl cis–trans isomerase A | 34 | A0A0G2K1P0 | NC |
175 | Cyclin-dependent kinase 2-interacting protein | 108 | B0BNM8 | DOWN |
176 | Rho GTPase-activating protein 23 | 684 | F1M2D4 | DOWN |
177 | Rho GTPase-activating protein 24 | 685 | F1M2D4 | DOWN |
178 | Rho GTPase-activating protein 20 | 1052 | Q6REY9 | NC |
179 | Rho GTPase-activating protein 20 | 1054 | Q6REY9 | NC |
Gene Symbol | Functional Annotations | |
---|---|---|
1 | Sdha | Succinate dehydrogenase is a mitochondrial flavoprotein (FP), a subunit of succinate dehydrogenase (SDH), which participates in the electron transport chain process of mitochondria. |
2 | Myl9 | Myosin regulatory light polypeptide 9 plays an important role in the regulation of smooth muscle and nonmuscle cell contractility through a phosphorylation-dependent manner. Additionally, it plays an important role in other cellular processes like cell division, cell movement, and receptor capping. |
3 | Ndufa5 | NADH dehydrogenase 1 alpha subcomplex subunit 5 constitutes the NADH dehydrogenase Complex I and helps in the transfer of electrons from NADH to the respiratory chain. |
4 | Atp5f1a | ATP synthase subunit alpha is a mitochondrial membrane protein. It generates ATP using the proton gradient of the membrane. |
5 | Eno1 | Alpha-enolase is a glycolytic enzyme that produces phosphoenolpyruvate from 2 phosphoglycerate. It regulates several cellular functions, including cellular growth, hypoxia, biochemical reactions, allergic reactions, etc. |
6 | Ryr3 | Ryanodine receptor 3 regulates the cellular calcium and contractility of cells. |
7 | Zfp821 | Zinc finger protein 821 is a nuclear DNA-binding protein. |
8 | RGD1597339 | The function of RCG48016, isoform CRAc, is not known. |
9 | Igf1 | Insulin-like growth factor I functions similarly to insulin but shows higher growth-promoting activity. It may participate in the transport of glucose and glycogen synthesis. |
10 | Alpk2 | Alpha-kinase 2 plays an important role in DNA repair and cellular apoptosis. |
11 | Clybl | Citramalyl-CoA lyase regulates the vitamin B12 metabolism. It also regulates the cellular detoxification process through detoxifying itaconate. Additionally, it also catalyzes the malate and beta-methyl malate synthesis in vitro. |
12 | Fgf8 | Fibroblast growth factor is a heparin-binding protein. It plays an important role in embryonic development, cell proliferation, cell differentiation, and cell migration. Additionally, it is required for the development of the gonadotropin-releasing hormone neuronal system. |
13 | Odf2 | Outer dense fiber protein 2 is an important component of the mammalian sperm tail and regulates sperm motility. It also functions as a general scaffold protein on the distal/subdistal appendages of the mother centrioles. |
14 | Myh10 | Myosin-10 regulates the stabilization of type I collagen mRNAs by interaction with the LARP6. It plays an important role in cytoskeleton reorganization and regulates lamellipodial extension, cell division, and cell shape. |
15 | Pdha1 | Pyruvate dehydrogenase E1 component subunit alpha is a mitochondrial protein and regulates cellular glycolytic and TCA cycles. |
16 | Zfp326 | Zinc finger protein 326 belongs to the AKAP95 family. |
17 | Actb | Actin forms cross-linked networks in the cell’s cytoplasm. Its monomeric (G-actin) and polymeric (F-actin) forms regulate cell motility and contraction in the cytoplasmic cytoskeleton. Nuclear actin regulates gene transcription, motility, and repair of damaged DNA. |
18 | Olr1625 | This is an olfactory receptor and belongs to the G-protein-coupled receptor. |
19 | Barx2 | BARX homeobox 2 is a DNA-binding transcriptional factor. It regulates the expression of neural adhesion molecules such as L1 or Ng-CAM during the embryonic development of the nervous system. |
20 | Hnrnpa1 | Heterogeneous nuclear ribonucleoprotein A1 regulates the packaging of pre-mRNA into hnRNP particles. It also regulates the transport and splicing of mRNA. |
21 | Bbox1 | Gamma-butyrobetaine dioxygenase regulates the L-carnitine formation from gamma- butyrobetaine. |
22 | H4f3 | This is histone cluster 1 H1 family member d. |
23 | Hand1 | Heart- and neural crest derivative-expressed protein 1 is a transcriptional factor, regulates cell differentiation, and is involved in cardiac morphogenesis. It also acts as a transcriptional repressor of the SOX15 gene, involved in cardiac oncogenesis. |
24 | Jmjd1c | Jumonji domain-containing 1C histone demethylase plays an important role in histone code via the demethylation of Lys-9 of histone H3. |
25 | Hmga1 | High mobility group protein HMG-I/HMG-Y preferably binds with the A- and T-rich double-stranded DNA. These proteins could function in nucleosome phasing and in the 3′-end processing of mRNA transcripts. Additionally, it regulates the transcription of genes belonging to the HMGA family. |
26 | Ppia | Peptidyl-prolyl cis–trans isomerase is involved in several cellular functions including protein folding, cellular apoptosis and cell death, platelet activation and aggregation, ROS production, and clearance of protein aggregates. |
27 | Olr331 | Olfactory receptor belongs to G-protein-coupled receptors. This helps in the initiation of neuronal response that helps in the perception of a smell. |
28 | H2bu1 | Histone H2B belongs to the histone H2B family. |
29 | Sdhb | Succinate dehydrogenase iron–sulfur subunit is a mitochondrial protein involved in mitochondrial electron transport and energy production. It also regulates the oxygen-related gene transcription through the production of succinate. Succinate is an oxygen sensor that stabilizes the hypoxia-inducible factor 1 (HIF1). |
30 | Gnas | Neuroendocrine secretory protein 55 belongs to the NESP55 family. This protein is involved in cellular signal transduction through G-protein-coupled receptors. |
31 | Ptma | Prothymosin alpha is an N-terminally processed protein found to be localized in the nucleus, cytoplasm, and extracellular environments. It regulates several cellular processes, including chromatin remodeling, transcription regulation, and inhibition of cellular apoptosis by blocking apoptosome formation. |
32 | Capn6 | Calpain-6 is a microtubule-stabilizing protein that could regulate cytoskeletal organization and microtubule dynamics. It may also control lamellipodial formation and cell mobility, but it does not seem to have any protease activity. |
33 | Zdhhc3 | Palmitoyltransferase helps in palmitoyltransferase activity. Zdhhc3 protein was found to be localized in the Golgi apparatus, and it is involved in several cellular functions, including TRAIL-activated apoptosis and protein localization in the membrane. |
34 | Arhgap23 | Rho GTPase-activating protein 23 is a small GTPase and is involved in signal transduction through transmembrane receptors. Arhgap23 has an inactive GDP-bound form and an active GTP-bound form. It regulates the activity of RHO family proteins by stimulating their hydrolysis of GTP. |
35 | Hist1h4b | This is Histone H4-like. |
36 | Crebbp | Crebbp regulates histone acetylation by its histone lysine acetyltransferase activity and regulates cellular gene expression in association with the CREB. It plays a critical role in cellular growth and division. |
37 | Ro60 | Ro60 is an RNA-binding protein that binds with the misfolded non-coding RNAs. It regulates the folding and degradation of non-coding RNAs. |
38 | Vegfa | Vascular endothelial growth factor A regulates several cellular functions, including angiogenesis, vasculogenesis, endothelial cell growth, and vascular permeability during lactation. |
39 | Lars1 | Lars1 functions as a cytosolic leucine–tRNA synthetase and catalyzes the ligation of L-leucine to tRNA (Leu). Additionally, it activates mTORC1 in a leucine-dependent manner. |
40 | Lrrc69 | This is leucine-rich repeat-containing 69. |
41 | Got2 | Aspartate aminotransferase is involved in amino acid metabolism and metabolite exchange between the mitochondria and cytosol. It helps the uptake of long-chain free fatty acids. |
42 | Rsf1 | Remodeling and spacing factor 1 is a histone chaperone and, in association with several other cellular ATPases, regulates chromatin remodeling and gene expression. |
43 | Aco2 | Aconitate hydratase is a mitochondrial aconitase/IPM isomerase family of proteins that catalyzes the biochemical reaction of the isomerization of citrate to isocitrate via cis-aconitate. |
44 | Nat10 | RNA cytidine acetyltransferase is an RNA cytidine acetyltransferase that catalyzes the formation of N(4)-acetylcytidine in 18S rRNA. |
45 | Myh6 | Alpha-myosin heavy chain (alpha-MHC) is primarily expressed in the cardiomyocytes. It is a major building block of sarcomeres and regulates cardiomyocyte contractility. |
46 | Ppif | Peptidyl-prolyl cis–trans isomerase F is a mitochondrial protein that accelerates protein folding through catalyzation of the cis–trans isomerization of proline imidic peptide bonds. Additionally, it is involved in regulating the mitochondrial permeability transition pore (mPTP). |
47 | Mdh2 | Malate dehydrogenase is a mitochondrial protein. It plays a critical role in cellular metabolic coordination between the cytosol and mitochondria by catalyzing the reversible oxidation of malate to oxaloacetate. |
48 | Nnt | Nicotinamide nucleotide transhydrogenase (NNT) is an inner mitochondrial membrane protein. This enzyme couples the proton flow by hydride transfer from NAD(H) to NADP(+). Additionally, during adverse conditions, it helps maintain mitochondrial membrane potential via proton pumping. |
49 | Tcp1 | T-complex protein 1 subunit alpha is a chaperone protein and helps in the folding of several cellular proteins such as RAP53/TCAB, actin, and tubulin. |
50 | Cox4i1 | Cytochrome c oxidase subunit 4 isoform 1 is a mitochondrial protein that is a component of the cytochrome c oxidase and plays an important role in oxidative phosphorylation. |
51 | Atp5pd | ATP synthase subunit d is a mitochondrial protein in Complex V that produces ATP from ADP in the presence of a proton gradient across the membrane. |
52 | Myl4 | Myosin light chain 4 is the regulatory light chain of myosin and an important part of sarcomeres. It helps in the cross-bridge kinetics of sarcomeres by allowing force generation. |
53 | Naa50 | This is a highly conserved eukaryotic N-terminal acetyltransferase found to be localized in the nucleoplasm. It helps in chromosome segregation during mitosis. Additionally, it acetylates beta-tubulin. |
54 | Smc3 | Structural maintenance of chromosome protein 3 is the central component of cohesion and plays a critical role in the cell cycle. It also takes part in DNA replication, repair, and spindle pole assembly during mitosis and in chromosome movement. |
55 | Pdhb | This is a subunit E1 component of the pyruvate dehydrogenase complex and localizes to mitochondria. It plays an important role in cellular metabolism by linking glycolysis and cellular ATP production via decarboxylation of pyruvate and generation of acetyl-CoA and CO2. |
56 | Slc25a4 | ADP/ATP translocase 1 is involved in mitochondrial ADP/ATP transport and catalyzes the exchange of cytoplasmic ADP with mitochondrial ATP across the inner mitochondrial membrane. |
57 | Myl2 | Myosin regulatory light chain 2 is an important component of the cardiomyocyte contractile apparatus. It plays an important role in cardiac muscle contraction through cross-bridge formation and force generation. |
58 | Pdhx | The pyruvate dehydrogenase complex component X is a mitochondrial noncatalytic component of PDH. It binds with subunit E3 of the PDH complex protein and regulates the conversion of pyruvate to acetyl coenzyme, linking glycolysis to the Krebs cycle. |
59 | Jpt1 | Jupiter microtubule-associated homolog 1 negatively modulates AKT-mediated GSK3B signaling. It also regulates other cellular functions like the cell cycle and cell adhesion and inhibits AR signaling through the degradation of receptors. |
60 | Glud1 | Glutamate dehydrogenase 1 is a mitochondrial glutamate dehydrogenase that converts L- glutamate into alpha-ketoglutarate. It plays an important role in glutamine anaplerosis by producing alpha-ketoglutarate. This is an intermediate in the tricarboxylic acid cycle. |
61 | Ywhaz | 14-3-3 protein zeta/delta plays a critical role in cellular signaling by regulating the activity of ARHGEF7 through binding with the phosphoserine or phosphothreonine motif of the protein. It also helps in cellular maturation. |
62 | Myl3 | Myosin light chain 3 is a regulatory light chain of myosin. It regulates the cardiac muscle contraction and muscle filament sliding. Mutation of this protein causes cardiac hypertrophy. |
63 | Rpl14 | 60S ribosomal protein L14 is a component of the large ribosomal subunit that belongs to the eukaryotic ribosomal protein eL14 family. |
64 | Tpm1 | The tropomyosin alpha-1 chain is an actin–myosin binding protein and regulates muscle contraction through cross-bridge formation. |
65 | Eef1g | Elongation factor 1-gamma is an important regulatory protein of cells, which helps in the translation of protein through the delivery of aminoacyl tRNAs to the ribosome during the elongation step. |
66 | Vdac3 | Voltage-dependent anion-selective channel protein 3 is a mitochondrial membrane protein and regulates mitochondrial diffusion of small hydrophilic molecules. |
67 | Cryab | Alpha-crystallin B chain is a chaperonic protein and is involved in protein folding. |
68 | Anxa6 | Annexin A6 is a protein that may associate with CD21 and regulate the release of Ca(2+) from intracellular stores. This protein belongs to the annexin family. |
69 | Akr1b1 | Aldo-keto reductase family 1 member B1 catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. |
70 | Crat | Carnitine O-acetyltransferase acts as a catalyst for the reversible transfer of acyl groups from carnitine to coenzyme A and regulates the ratio of acyl-CoA/CoA. It also plays a crucial role in the transport of fatty acids for beta-oxidation and it may be specific for short-chain fatty acids. |
71 | Mrpl47 | Mitochondrial ribosomal protein L47 plays an important role in mitochondrial translational and metabolism of proteins. |
72 | Hspe1 | This is a 10 kDa heat shock protein that is in the mitochondria. It is a co-chaperonin implicated in mitochondrial protein import and macromolecular assembly. It coordinates with Hsp60 and facilitates the correct folding of imported proteins. Additionally, during cellular stress, this protein binds with the unfolded protein and helps in proper folding. |
73 | Ak3 | GTP:AMP phosphotransferase AK3 is a mitochondrial protein that catalyzes the interconversion of nucleoside phosphates and is involved in maintaining the homeostasis of cellular nucleotides. It performs GTP to AMP phosphotransferase and ITP to AMP phosphotransferase activities. |
74 | Rbbp4 | RB-binding protein 4 is a chromatin-remodeling factor. It promotes the repression of gene expression through binding with several chromatin regulatory factors including histone deacetylases. |
75 | H2az1 | Histone H2A.Z is a histone protein that regulates DNA folding and gene transcription. |
76 | Lgals1 | Galectin-1 is a lectin that binds beta-galactosidase and a different class of carbohydrates. It plays an important role in the different cellular functions including apoptosis, cell proliferation, and cell differentiation. This protein helps to maintain the phosphorylation of Lyn kinase by inhibiting the phosphatase activity of CD45. |
77 | Rrbp1 | Ribosome-binding protein 1 is an endoplasmic reticulum protein and helps in ER proliferation, secretion, and cell differentiation. |
78 | Dld | Dihydrolipoyl dehydrogenase is a mitochondrial protein and part of three enzymes: (i) branched-chain alpha-ketoacid dehydrogenase complexes (BCKDH), (ii) alpha-ketoacid dehydrogenase complexes (αKGDH), and (iii) pyruvate dehydrogenase (PDH) complex. It mainly regulates cellular energy metabolism as well as lysine succinylation of histones in the nucleus. |
79 | Myh9 | Myosin-9 plays an important role in cytoskeleton reorganization and regulates cell division, shape, and secretion. |
80 | Shmt2 | Serine hydroxymethyltransferase regulates the interconversion of serine and glycine and belongs to the SHMT family. |
81 | Hadha | Trifunctional enzyme subunit alpha is a mitochondrial enzyme that catalyzes the last three reactions in the mitochondrial beta-oxidation pathway. It helps in the energy production of the tissue through mitochondria by helping in the four consecutive breaking down reactions of fatty acids into acetyl-CoA. |
82 | Echs1 | Enoyl-CoA hydratase is a mitochondrial enzyme. Straight-chain enoyl-CoA thioesters from C4 to at least C16 are processed by decreasing the catalytic rate. This enzyme acts on substrates like crotonyl-CoA, acryloyl-CoA, 3-methylcrotonyl-CoA, and methacrylyl-CoA. |
83 | Sh2d3c | This protein contains a guanine nucleotide exchange factor-like domain, which binds with the Ras family of GTPases and acts as an adaptor protein. It is involved in cell migration. |
84 | Ywhaq | 14-3-3 protein theta is an adapter protein that regulates the kinase activity of PDPK1. |
85 | Uqcrc2 | Cytochrome b-c1 complex subunit 2 is a mitochondrial protein and regulates mitochondrial electron transport chain reaction through the formation of the ubiquinol–cytochrome c reductase complex (complex III). |
86 | Rabepk | This is a Rab9 effector protein having kelch motifs. It is involved in receptor-mediated endocytosis and vesicle docking, which are involved in exocytosis. |
87 | Sox7 | SRY-box containing gene 7 acts as a transcription factor. It forms complex with other cellular proteins and regulates embryonic development and cellular fate. |
88 | Cep295 | The centrosomal protein of 295 kDa is a centriole-enriched microtubule-binding protein. This protein is localized in the cytosol microtubule and plasma membrane and positively regulates protein acetylation. |
89 | Myl6 | Myosin light polypeptide 6 is a regulatory light chain of myosin. This protein plays a key role in cellular movement by helping in force generation. Additionally, it is involved in muscle contraction, platelet activation, cell viability, vesicle-mediated cargo transport, endocytosis, and cancer cell progression. |
90 | Lrif1 | This protein belongs to the LRIF1 family. It localizes to the centriolar satellite, nucleoplasm, chromosome, telomeric region, and nuclear lumen. In females, it acts as a repressor of chromosome X. Additionally, it represses the function of retinoic acid alpha through direct recruitment of histone deacetylase. |
91 | Il16 | Pro-interleukin-16 stimulates a migratory response in CD4+ lymphocytes, monocytes, and eosinophils. It also primes CD4+ T-cells for IL-2 and IL-15 responsiveness and induces T-lymphocyte expression of interleukin 2 receptor. It is a ligand for CD4. |
92 | Gtf3c1 | General transcription factor 3C polypeptide 1 is an important component of RNA polymerase and regulates transcription. |
93 | Rps9 | 40S ribosomal protein S9 belongs to the universal ribosomal protein uS4 family. This protein plays an important role in ribosome biogenesis, translation, cell growth and proliferation, apoptosis, DNA repair, and developmental regulations. |
94 | Eci2 | Enoyl-CoA delta isomerase 2 is a mitochondrial enzyme that is able to isomerize both 3-cis and 3-trans double bonds into the 2-trans form in a range of enoyl-CoA species. Additionally, it is involved in lipid metabolism and promotes cancer cell survival. |
95 | Arhgap20 | Rho GTPase-activating protein 20 is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. |
96 | Tmem176b | Transmembrane protein 176B is required for the development of cerebellar granule cells and it may regulate the maturation of dendritic cells. |
97 | Tspy1 | Testis-specific Y-encoded protein is involved in cellular metabolism such as spermatogenesis, cell proliferation, and androgen signaling. |
98 | Cinp | This is potentially similar to the cyclin-dependent kinase 2-interacting protein, isoform CRA_a. This protein regulates ATR-dependent signaling, resistance to stress, and G2 checkpoint integrity. |
99 | Spag17 | Sperm-associated antigen 17 is associated with several cellular functions such as germ cell differentiation, bone development, structure and motility of cilia, and nuclear translocation of protamines. |
100 | Angptl3 | Angiopoietin-like 3 isoform CRA_b plays an important role in lipoprotein metabolism. |
101 | Mrpl3 | 39S ribosomal protein L3 localizes to mitochondria and belongs to the universal ribosomal protein uL3 family. It is involved in the biosynthesis of mitochondrial protein and the structure and biogenesis of ribosomes. |
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Rajakumar, A.; Nguyen, S.; Ford, N.; Ogundipe, G.; Lopez-Nowak, E.; Kondrachuk, O.; Gupta, M.K. Acetylation-Mediated Post-Translational Modification of Pyruvate Dehydrogenase Plays a Critical Role in the Regulation of the Cellular Acetylome During Metabolic Stress. Metabolites 2024, 14, 701. https://doi.org/10.3390/metabo14120701
Rajakumar A, Nguyen S, Ford N, Ogundipe G, Lopez-Nowak E, Kondrachuk O, Gupta MK. Acetylation-Mediated Post-Translational Modification of Pyruvate Dehydrogenase Plays a Critical Role in the Regulation of the Cellular Acetylome During Metabolic Stress. Metabolites. 2024; 14(12):701. https://doi.org/10.3390/metabo14120701
Chicago/Turabian StyleRajakumar, Aishwarya, Sarah Nguyen, Nicole Ford, Gbenga Ogundipe, Ethan Lopez-Nowak, Olena Kondrachuk, and Manish K Gupta. 2024. "Acetylation-Mediated Post-Translational Modification of Pyruvate Dehydrogenase Plays a Critical Role in the Regulation of the Cellular Acetylome During Metabolic Stress" Metabolites 14, no. 12: 701. https://doi.org/10.3390/metabo14120701
APA StyleRajakumar, A., Nguyen, S., Ford, N., Ogundipe, G., Lopez-Nowak, E., Kondrachuk, O., & Gupta, M. K. (2024). Acetylation-Mediated Post-Translational Modification of Pyruvate Dehydrogenase Plays a Critical Role in the Regulation of the Cellular Acetylome During Metabolic Stress. Metabolites, 14(12), 701. https://doi.org/10.3390/metabo14120701