目录号 | 产品详情 | 靶点 | |
---|---|---|---|
T76536 | |||
Pinealon是一种由三个氨基酸构成的肽,展现出神经保护属性。该化合物能够抑制ROS(活性氧)的积累和ERK1/2活化,激发脑组织主要细胞成分的活跃性,减缓自发性细胞凋亡率。此外,Pinealon对于防护大鼠后代免遭产前高同型半胱氨酸血症的影响亦显著。 | |||
T72475 | |||
Anticancer agent 58 对多种癌细胞具有抑制活性,特别是在 A549 和 T24 细胞中,IC50分别为 0.6 μM 和 0.7 μM。Anticancer agent 58 通过激活 caspase3/8/9活性诱导细胞凋亡 (apoptosis),也诱导 Ca2+和 ROS 水平升高。Anticancer agent 58 在 T24 异种移植小鼠模型中能显著抑制肿瘤生长。 | |||
T79739 | |||
CYP51/PD-L1-IN-2(compound L20)是一种具有抗真菌活性的喹唑啉化合物。它作为CYP51(IC50:0.263 μM)和PD-L1(IC50:0.017 μM)的双重抑制剂,能够在细胞周期的早期引发真菌细胞凋亡。CYP51/PD-L1-IN-2进一步显著降低IL-2、NLRP3、NF-κBp65等蛋白水平,触发线粒体损伤及ROS积累,终致真菌细胞裂解和死亡。 | |||
T62284 | |||
Anti-inflammatory agent 21 (compound 9o) 是一种低细胞毒性的、口服具有活力的抗炎剂,能够作用于 NO (IC50: 0.76 μM)。Anti-inflammatory agent 21 能够积累 ROS、阻断 NF-κB/MAPK 信号通路来发挥抗炎作用。 Anti-inflammatory agent 21 对关节炎大鼠模型的软骨破坏和炎症细胞浸润有一定的改善作用。 | |||
T36330 | |||
Terrecyclic acid is a sesquiterpene originally isolated from A. terreus with antibiotic and anticancer activity. It is active against S. aureus, B. subtilis, and M. roseus (MICs = 25, 50, and 25 μg/ml, respectively). Terrecyclic acid induces a heat shock response, increases levels of reactive oxygen species (ROS), and inhibits NF-κB activity and cell growth in 3T3-Y9-B12 cells. In vivo, terrecyclic acid (0.1, 1, and 10 mg/ml) reduces the number of ascitic fluid tumor cells in a mouse model of P388 murine leukemia. | |||
T81249 | PARP | ||
Ru3是一种poly(ADP-ribose)polymerase 1抑制剂,能够通过诱导DNA损伤、抑制DNA修复机制、扰乱细胞周期、降低线粒体膜电位及增加reactive oxygen species水平来诱导MCF-7细胞的apoptosis。 | |||
T73125 | HSP | ||
SMTIN-T140(化合物6a)是一种TRAP1(肿瘤坏死因子受体相关蛋白1)的高效抑制剂,IC50值为1.646 μM。该化合物表现出显著的抗癌活性,可引起线粒体功能障碍,增加线粒体ROS产生以及激活AMPK。在PC3前列腺癌细胞异种移植的小鼠模型中,SMTIN-T140有效抑制了肿瘤生长,并显示出良好的体内安全性。 | |||
T81485 | |||
Phoenixin-14 (PNX-14) TFA 是具抗焦虑、心脏保护及神经保护效果的穿透大脑屏障神经肽。它通过上调GnRH受体mRNA调控垂体促性腺激素分泌,并促进胰岛素释放。此外,Phoenixin-14 TFA保护小鼠免受缺血/再灌注(IR)伤害,通过降低ROS、提高GSH减缓氧化应激。 | |||
T74501 | |||
NHEJ inhibitor-1 (Compound C2) 是一种三功能 Pt(II) 复合物,可缓解非同源末端连接 (NHEJ)/同源重组 (HR) 相关的双链断裂 (DSB) 修复,从而避免非小细胞肺对顺铂的耐药性。NHEJ inhibitor-1 抑制损伤修复蛋白 Ku70 和 Rad51,从而使肿瘤对活性分子重新敏感。NHEJ inhibitor-1 还诱导 ROS 产生和MMP 降低。 | |||
T81867 | Autophagy | ||
MAO-B-IN-26(Compound IC9)是一种双重功能抑制剂,针对MAO-B和乙酰胆碱酯酶进行抑制。它能有效地防护SH-SY5Y细胞,对抗由Aβ引起的细胞毒性、形态学变化、反应性氧(ROS)产生和膜损伤。此外,MAO-B-IN-26还可抑制Aβ触发的自噬(autophagy)和细胞凋亡(apoptosis),具备作为治疗阿尔茨海默病的神经保护剂的潜力。 |
目录号 | 产品名/同用名 | 种属 | 表达系统 | ||
---|---|---|---|---|---|
TMPY-05001 | MPZL3 Protein, Human, Recombinant (His) | Human | HEK293 Cells | ||
MPZL3 (Myelin Protein Zero Like 3) is a Protein Coding gene. The encoded protein belongs to the myelin P0 protein family. MPZL3 is broadly expressed in skin, esophagus, and other tissues. MPZL3 was essential for normal differentiation, acting downstream of p63, ZNF750, KLF4, and RCOR1, each of which bound near the MPZL3 gene and controlled its expression. MPZL3 protein localized to mitochondria, where it interacted with FDXR, which was itself also found to be essential for differentiation. Together, MPZL3 and FDXR increased reactive oxygen species (ROS) to drive epidermal differentiation. ROS-induced differentiation is dependent upon the promotion of FDXR enzymatic activity by MPZL3. ROS induction by the MPZL3 and FDXR mitochondrial proteins is therefore essential for epidermal differentiation.
|
|||||
TMPH-02106 | SH3PXD2A Protein, Human, Recombinant (His & Myc) | Human | E. coli | ||
Adapter protein involved in invadopodia and podosome formation, extracellular matrix degradation and invasiveness of some cancer cells. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. In association with ADAM12, mediates the neurotoxic effect of amyloid-beta peptide.
|
|||||
TMPH-02875 | ROMO1 Protein, Mouse, Recombinant (His) | Mouse | E. coli | ||
Has antibacterial activity against a variety of bacteria including S.aureus, P.aeruginosa and M.tuberculosis. Acts by inducing bacterial membrane breakage.; Induces production of reactive oxygen species (ROS) which are necessary for cell proliferation. May play a role in inducing oxidative DNA damage and replicative senescence. May play a role in the coordination of mitochondrial morphology and cell proliferation.
|
|||||
TMPH-02681 | GPX7 Protein, Mouse, Recombinant (His & Myc) | Mouse | E. coli | ||
It protects esophageal epithelia from hydrogen peroxide-induced oxidative stress. It suppresses acidic bile acid-induced reactive oxigen species (ROS) and protects against oxidative DNA damage and double-strand breaks. GPX7 Protein, Mouse, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 26.7 kDa and the accession number is Q99LJ6.
|
|||||
TMPH-02104 | Sestrin-3/SESN3 Protein, Human, Recombinant (His & Myc) | Human | E. coli | ||
May function as an intracellular leucine sensor that negatively regulates the TORC1 signaling pathway. May also regulate the insulin-receptor signaling pathway through activation of TORC2. This metabolic regulator may also play a role in protection against oxidative and genotoxic stresses. May prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein.
|
|||||
TMPH-00099 | NDK1 Protein, Arabidopsis thaliana, Recombinant (His & Myc) | Arabidopsis thaliana | P. pastoris (Yeast) | ||
Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Plays a role in response to reactive oxygen species (ROS) stress. NDK1 Protein, Arabidopsis thaliana, Recombinant (His & Myc) is expressed in yeast with N-10xHis and C-Myc tag. The predicted molecular weight is 20.5 kDa and the accession number is P39207.
|
|||||
TMPH-02658 | FPR1 Protein, Mouse, Recombinant (GST & His & Myc) | Mouse | E. coli | ||
High affinity receptor for N-formyl-methionyl peptides (fMLP), which are powerful neutrophil chemotactic factors. Binding of fMLP to the receptor stimulates intracellular calcium mobilization and superoxide anion release. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Receptor for TAFA4, mediates its effects on chemoattracting macrophages, promoting phagocytosis and increasing ROS release. FPR1 Protein, Mouse, Recombinant (GST & His & Myc) is expressed in E. coli expression system with N-10xHis-GST and C-Myc tag. The predicted molecular weight is 33.7 kDa and the accession number is P33766.
|
|||||
TMPH-01346 | FPR1 Protein, Human, Recombinant (GST & His & Myc) | Human | E. coli | ||
High affinity receptor for N-formyl-methionyl peptides (fMLP), which are powerful neutrophil chemotactic factors. Binding of fMLP to the receptor stimulates intracellular calcium mobilization and superoxide anion release. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Receptor for TAFA4, mediates its effects on chemoattracting macrophages, promoting phagocytosis and increasing ROS release. FPR1 Protein, Human, Recombinant (GST & His & Myc) is expressed in E. coli expression system with N-10xHis-GST and C-Myc tag. The predicted molecular weight is 34.9 kDa and the accession number is P21462.
|
|||||
TMPY-02271 | TRXR1/TXNRD1 Protein, Human, Recombinant (aa 161-647, His) | Human | E. coli | ||
Thioredoxin reductase 1 (TXNRD1) which is a selenocysteine-containing protein is overexpressed in many malignancies. TXNRD1 plays a key role in regulating cell growth and transformation, and protects cells against oxidative damage. We investigated the association between TXNRD1 polymorphisms and ATDH susceptibility. Moreover, TXNRD1 is an essential selenium-containing enzyme involved in detoxification of reactive oxygen species (ROS) and redox signaling. And genetic variations in TXNRD1 favor the development of Drug-induced liver injury (DILI), which is the most common adverse drug reaction.
|
|||||
TMPJ-00933 | PRDX5 Protein, Human, Recombinant (His) | Human | HEK293 Cells | ||
Peroxisomes are essential organelles that participate in multiple important metabolic processes, including the β-oxidation of fatty acids, plasmalogen synthesis, and the metabolism of reactive oxygen species (ROS). Peroxiredoxins is overexpressed in breast cancer tissues to a great extent suggesting that they has a proliferative effect and may be related to cancer development or progression. Peroxiredoxin 5 (PRDX5) is a thioredoxin peroxidase that belongs to the atypical 2-Cys class of the TSA/ahpC family of peroxiredoxins. PRDX5 is a widely expressed mitochondrial antioxidant enzyme that reduces hydrogen peroxide, alkyl hydroperoxides, and peroxynitrite. In human cells, this enzyme is present in the cytosol, mitochondria, peroxisomes, and nucleus.
|
|||||
TMPH-02585 | ACOD1 Protein, Mouse, Recombinant (His & Myc) | Mouse | Baculovirus Insect Cells | ||
Cis-aconitate decarboxylase that catalyzes production of itaconate and is involved in the inhibition of the inflammatory response. Acts as a negative regulator of the Toll-like receptors (TLRs)-mediated inflammatory innate response by stimulating the tumor necrosis factor alpha-induced protein TNFAIP3 expression via reactive oxygen species (ROS) in LPS-tolerized macrophages. Involved in antimicrobial response of innate immune cells; ACOD1-mediated itaconic acid production contributes to the antimicrobial activity of macrophages. Involved in antiviral response following infection by flavivirus in neurons: ACOD1-mediated itaconate production inhibits the activity of succinate dehydrogenase, generating a metabolic state in neurons that suppresses replication of viral genomes. Plays a role in the embryo implantation.
|
|||||
TMPJ-01274 | ERO1L Protein, Human, Recombinant (His) | Human | HEK293 Cells | ||
ERO1-Like Protein α (ERO1L) is an enzyme that belongs to the EROs family. ERO1L is expressed at high level in esophagus and upper digestive tract. ERO1L is an essential oxidoreductase that oxidizes proteins in the endoplasmic reticulum to produce disulfide bonds. ERO1L acts by oxidizing directly P4HB/PDI isomerase through a direct disulfide exchange. It associates with ERP44, demonstrating that it does not oxidize all PDI related proteins and can discriminate between PDI and related proteins. Its reoxidation probably involves electron transfer to molecular oxygen via FAD. ERO1L may be responsible for a significant proportion of reactive oxygen species (ROS) in the cell. ERO1L responses to temperature stimulus, protein thiol-disulfide exchange, protein folding with or without chaperone cofactor and transport.
|
|||||
TMPH-02264 | TNFSF11 Protein, Human, Recombinant (His) | Human | HEK293 Cells | ||
Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy. Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation.
|
|||||
TMPY-02391 | SUMO1 Protein, Human, Recombinant (His) | Human | E. coli | ||
Small ubiquitin-like modifier protein (SUMO) modification is a highly dynamic process, catalyzed by SUMO-specific activating (E1), conjugating (E2) and ligating (E3) enzymes, and reversed by a family of SUMO-specific proteases (SENPs). Small ubiquitin-like modifier 1 (SUMO1) is a member of the superfamily of ubiquitin-like proteins. Despite its structural similarity with ubiquitin, SUMO1 does not seem to play any role in protein degradation. SUMO1 plays an important role in modulation of NOX activity required for ROS generation. SUMO1 haploinsufficiency results in cleft lip and palate in animal models. SUMO1 gene variation in human non-syndromic cleft lip with or without cleft palate (NSCLP) development. SUMO-1 may be useful as a novel target for therapy in oral squamous cell carcinoma (SCC) as well as a clinical indicator for tumor recurrence together with Mdm2.
|
|||||
TMPY-02084 | Thioredoxin 2/TRX2 Protein, Human, Recombinant (His) | Human | E. coli | ||
Thioredoxin-2, also known as TXN2, MTRX and TRX2, is a member of the thioredoxin family. Tryparedoxins (TXN) are thioredoxin-related proteins which, as trypanothione:peroxiredoxin oxidoreductases, constitute the trypanothione-dependent antioxidant defense and may also serve as substrates for ribonucleotide reductase in trypanosomatids. Thioredoxin-2 / TXN2 contains one thioredoxin domain. It is widely expressed in adult (at protein level) and fetal tissues. Human Thioredoxin-2 / TXN2 is a small redox protein important in cellular antioxidant defenses, as well as in the regulation of apoptosis. Thioredoxin-2 / TXN2 has an anti-apoptotic function and plays an important role in the regulation of mitochondrial membrane potential. Thioredoxin-2 / TXN2 could be involved in the resistance to anti-tumor agents. It possesses a dithiol-reducing activity. Thioredoxin-2 / TXN2 plays an important role in protecting the mitochondria against oxidative stress and in sensitizing the cells to ROS-induced apoptosis. Mammalian Thioredoxin-2 / TXN2 is a mitochondrial isoform of highly evolutionary conserved thioredoxins. Thioredoxins are small ubiquitous protein-disulfide oxidoreductases implicated in a large variety of biological functions.
|
|||||
TMPY-01770 | HAO1 Protein, Human, Recombinant (His) | Human | E. coli | ||
Hydroxyacid oxidase 1, also known as Glycolate oxidase, HAO1, and GOX1, is a member of the FMN-dependent alpha-hydroxy acid dehydrogenase family. HAO1 / GOX1 has 2-hydroxyacid oxidase activity. It is most active on the 2-carbon substrate glycolate, but is also active on 2-hydroxy fatty acids, with high activity towards 2-hydroxy palmitate and 2-hydroxy octanoate. HAO1 / GOX1 is a liver-specific peroxisomal enzyme that oxidizes glycolate to glyoxylate with the concomitant production of H2O2. In Hao1 messenger RNA (mRNA), an iron-responsive element (IRE) homologous to the sequence recognized by iron regulatory proteins (IRP), key regulators of iron homeostasis, is present. Mammalian HAO1 / GOX1 is a peroxisomal protein and that the C-terminal sequence SKI acts as the targeting signal. Down-regulation of HAO1 / GOX1 expression during oxidative stress may provide a mechanism to prevent excessive H2O2 formation in liver peroxisomes and may represent the prototype of a poorly recognized but potentially relevant response to an oxidative injury involving down-regulation of ROS-producing enzymes.
|
|||||
TMPY-04813 | ACAT2 Protein, Rat, Recombinant (His) | Rat | E. coli | ||
Acyl-coenzyme A: cholesterol acyltransferase (ACAT) is an intracellular enzyme that produces cholesteryl esters in various tissues. In mammals, two ACAT genes (ACAT1 and ACAT2) have been identified. Together, these two enzymes are involved in storing cholesteryl esters as lipid droplets, in macrophage foam-cell formation, in absorbing dietary cholesterol, and in supplying cholesteryl esters as part of the core lipid for lipoprotein synthesis and assembly. The key difference in tissue distribution of ACAT1 and ACAT2 between humans, mice and monkeys is that, in adult human liver (including hepatocytes and bile duct cells), the major enzyme is ACAT1, rather than ACAT2. There is compelling evidence implicating a role for ACAT1 in macrophage foam-cell formation, and for ACAT2 in intestinal cholesterol absorption.Ubiquitin linkage to cysteine is an unconventional modification targeting protein for degradation. However, the physiological regulation of cysteine ubiquitylation is still mysterious. Here we found that ACAT2, a cellular enzyme converting cholesterol and fatty acid to cholesteryl esters, was ubiquitylated on Cys277 for degradation when the lipid level was low. gp78-Insigs catalysed Lys48-linked polyubiquitylation on this Cys277. A high concentration of cholesterol and fatty acid, however, induced cellular reactive oxygen species (ROS) that oxidized Cys277, resulting in ACAT2 stabilization and subsequently elevated cholesteryl esters. Furthermore, ACAT2 knockout mice were more susceptible to high-fat diet-associated insulin resistance. By contrast, expression of a constitutively stable form of ACAT2 (C277A) resulted in higher insulin sensitivity. ACAT2 is an appealing target for therapy to reduce coronary heart disease.
|
|||||
TMPH-01263 | PRKN Protein, Human, Recombinant (His & SUMO) | Human | E. coli | ||
Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Substrates include SYT11 and VDAC1. Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components. Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy. Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin. After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis. When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30. Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy. The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2. This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes. Regulates motility of damaged mitochondria via the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma. Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A. Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress. Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene.
|
|||||
TMPH-02631 | PRKN Protein, Mouse, Recombinant (GST) | Mouse | E. coli | ||
Functions within a multiprotein E3 ubiquitin ligase complex, catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Substrates include SYT11 and VDAC1. Other substrates are BCL2, CCNE1, GPR37, RHOT1/MIRO1, MFN1, MFN2, STUB1, SNCAIP, SEPTIN5, TOMM20, USP30, ZNF746, MIRO1 and AIMP2. Mediates monoubiquitination as well as 'Lys-6', 'Lys-11', 'Lys-48'-linked and 'Lys-63'-linked polyubiquitination of substrates depending on the context. Participates in the removal and/or detoxification of abnormally folded or damaged protein by mediating 'Lys-63'-linked polyubiquitination of misfolded proteins such as PARK7: 'Lys-63'-linked polyubiquitinated misfolded proteins are then recognized by HDAC6, leading to their recruitment to aggresomes, followed by degradation. Mediates 'Lys-63'-linked polyubiquitination of a 22 kDa O-linked glycosylated isoform of SNCAIP, possibly playing a role in Lewy-body formation. Mediates monoubiquitination of BCL2, thereby acting as a positive regulator of autophagy. Protects against mitochondrial dysfunction during cellular stress, by acting downstream of PINK1 to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components. Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy. Activation and recruitment onto the outer membrane of damaged/dysfunctional mitochondria (OMM) requires PINK1-mediated phosphorylation of both PRKN and ubiquitin. After mitochondrial damage, functions with PINK1 to mediate the decision between mitophagy or preventing apoptosis by inducing either the poly- or monoubiquitination of VDAC1, respectively; polyubiquitination of VDAC1 promotes mitophagy, while monoubiquitination of VDAC1 decreases mitochondrial calcium influx which ultimately inhibits apoptosis. When cellular stress results in irreversible mitochondrial damage, promotes the autophagic degradation of dysfunctional depolarized mitochondria (mitophagy) by promoting the ubiquitination of mitochondrial proteins such as TOMM20, RHOT1/MIRO1, MFN1 and USP30. Preferentially assembles 'Lys-6'-, 'Lys-11'- and 'Lys-63'-linked polyubiquitin chains, leading to mitophagy. The PINK1-PRKN pathway also promotes fission of damaged mitochondria by PINK1-mediated phosphorylation which promotes the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2. This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes. Regulates motility of damaged mitochondria via the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma. Involved in mitochondrial biogenesis via the 'Lys-48'-linked polyubiquitination of transcriptional repressor ZNF746/PARIS which leads to its subsequent proteasomal degradation and allows activation of the transcription factor PPARGC1A. Limits the production of reactive oxygen species (ROS). Regulates cyclin-E during neuronal apoptosis. In collaboration with CHPF isoform 2, may enhance cell viability and protect cells from oxidative stress. Independently of its ubiquitin ligase activity, protects from apoptosis by the transcriptional repression of p53/TP53. May protect neurons against alpha synuclein toxicity, proteasomal dysfunction, GPR37 accumulation, and kainate-induced excitotoxicity. May play a role in controlling neurotransmitter trafficking at the presynaptic terminal and in calcium-dependent exocytosis. May represent a tumor suppressor gene.
|