Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2HL10J)

• DOT Name: Mitochondrial fission 1 protein (FIS1)
• Synonyms: FIS1 homolog; hFis1; Tetratricopeptide repeat protein 11; TPR repeat protein 11
• Gene Name: FIS1
• Related Disease:
  Acute kidney injury
  Acute monocytic leukemia
  Alzheimer disease
  Amyotrophic lateral sclerosis
  Autosomal dominant optic atrophy, classic form
  Chronic renal failure
  Diabetic kidney disease
  Glioma
  Huntington disease
  Neoplasm
  Osteoarthritis
  Rhinitis
  Acute myelogenous leukaemia
  High blood pressure
  Cardiomyopathy
  Melanoma
  Membranous glomerulonephritis
  Myocardial infarction
  Nephrotic syndrome
• UniProt ID: FIS1_HUMAN
• PDB ID: 1NZN; 1PC2; 7YA9; 7YKA
• Pfam ID: PF14853 ; PF14852
• Sequence:
  MEAVLNELVSVEDLLKFEKKFQSEKAAGSVSKSTQFEYAWCLVRSKYNDDIRKGIVLLEE
  LLPKGSKEEQRDYVFYLAVGNYRLKEYEKALKYVRGLLQTEPQNNQAKELERLIDKAMKK
  DGLVGMAIVGGMALGVAGLAGLIGLAVSKSKS
• Function: Involved in the fragmentation of the mitochondrial network and its perinuclear clustering. Plays a minor role in the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface and mitochondrial fission. May not be essential for the assembly of functional fission complexes and the subsequent membrane scission event. Also mediates peroxisomal fission. May act when the products of fission are directed toward mitochondrial homeostasis, mitophagy, or apoptosis. Can induce cytochrome c release from the mitochondrion to the cytosol, ultimately leading to apoptosis.
• KEGG Pathway: Mitophagy - animal (hsa04137)
• Reactome Pathway: Class I peroxisomal membrane protein import (R-HSA-9603798)

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute kidney injury	DISXZG0T	Definitive	Biomarker	[1]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[4]
Autosomal dominant optic atrophy, classic form	DISXUAV9	Strong	Genetic Variation	[5]
Chronic renal failure	DISGG7K6	Strong	Therapeutic	[6]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[7]
Glioma	DIS5RPEH	Strong	Biomarker	[8]
Huntington disease	DISQPLA4	Strong	Biomarker	[9]
Neoplasm	DISZKGEW	Strong	Altered Expression	[10]
Osteoarthritis	DIS05URM	Strong	Biomarker	[11]
Rhinitis	DISKLMN7	Strong	Biomarker	[12]
Acute myelogenous leukaemia	DISCSPTN	moderate	Altered Expression	[13]
High blood pressure	DISY2OHH	moderate	Biomarker	[14]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[15]
Melanoma	DIS1RRCY	Limited	Biomarker	[16]
Membranous glomerulonephritis	DISFSUKQ	Limited	Biomarker	[17]
Myocardial infarction	DIS655KI	Limited	Biomarker	[18]
Nephrotic syndrome	DISSPSC2	Limited	Biomarker	[17]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Mitochondrial fission 1 protein (FIS1) affects the response to substance of Mitomycin.	[35]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Mitochondrial fission 1 protein (FIS1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Mitochondrial fission 1 protein (FIS1).	[31]

16 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitochondrial fission 1 protein (FIS1).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Mitochondrial fission 1 protein (FIS1).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitochondrial fission 1 protein (FIS1).	[22]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Mitochondrial fission 1 protein (FIS1).	[23]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Mitochondrial fission 1 protein (FIS1).	[24]
Selenium	DM25CGV	Approved	Selenium increases the expression of Mitochondrial fission 1 protein (FIS1).	[25]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Mitochondrial fission 1 protein (FIS1).	[26]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Mitochondrial fission 1 protein (FIS1).	[27]
Efavirenz	DMC0GSJ	Approved	Efavirenz increases the expression of Mitochondrial fission 1 protein (FIS1).	[28]
Angiotensin Ii	DMLWQ27	Approved	Angiotensin Ii increases the expression of Mitochondrial fission 1 protein (FIS1).	[29]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Mitochondrial fission 1 protein (FIS1).	[30]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Mitochondrial fission 1 protein (FIS1).	[25]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Mitochondrial fission 1 protein (FIS1).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mitochondrial fission 1 protein (FIS1).	[32]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Mitochondrial fission 1 protein (FIS1).	[33]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Mitochondrial fission 1 protein (FIS1).	[34]

References

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• [10] Proviral insertions near cyclin D1 in mouse lymphomas: a parallel for BCL1 translocations in human B-cell neoplasms.Oncogene. 1992 Dec;7(12):2381-7.
• [11] Correction to: Fis1 depletion in osteoarthritis impairs chondrocyte survival and peroxisomal and lysosomal function.J Mol Med (Berl). 2019 Dec;97(12):1735. doi: 10.1007/s00109-019-01850-5.
• [12] PM(2.5)-Induced Oxidative Stress and Mitochondrial Damage in the Nasal Mucosa of Rats.Int J Environ Res Public Health. 2017 Jan 29;14(2):134. doi: 10.3390/ijerph14020134.
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• [16] Expression of mitochondrial dynamics markers during melanoma progression: Comparative study of head and neck cutaneous and mucosal melanomas.J Oral Pathol Med. 2019 May;48(5):373-381. doi: 10.1111/jop.12855. Epub 2019 Apr 10.
• [17] Overproduction of Mitochondrial Fission Proteins in Membranous Nephropathy in Children.Kidney Blood Press Res. 2018;43(6):1927-1934. doi: 10.1159/000496006. Epub 2018 Dec 14.
• [18] Autophagy signaling in skeletal muscle of infarcted rats.PLoS One. 2014 Jan 10;9(1):e85820. doi: 10.1371/journal.pone.0085820. eCollection 2014.
• [19] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [20] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [21] Expression Profiling of Human Pluripotent Stem Cell-Derived Cardiomyocytes Exposed to Doxorubicin-Integration and Visualization of Multi-Omics Data. Toxicol Sci. 2018 May 1;163(1):182-195. doi: 10.1093/toxsci/kfy012.
• [22] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [23] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [24] Tea polyphenols direct Bmal1-driven ameliorating of the redox imbalance and mitochondrial dysfunction in hepatocytes. Food Chem Toxicol. 2018 Dec;122:181-193.
• [25] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [26] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [27] Gingival Stromal Cells as an In Vitro Model: Cannabidiol Modulates Genes Linked With Amyotrophic Lateral Sclerosis. J Cell Biochem. 2017 Apr;118(4):819-828. doi: 10.1002/jcb.25757. Epub 2016 Nov 28.
• [28] Lon protease: a novel mitochondrial matrix protein in the interconnection between drug-induced mitochondrial dysfunction and endoplasmic reticulum stress. Br J Pharmacol. 2017 Dec;174(23):4409-4429. doi: 10.1111/bph.14045. Epub 2017 Nov 7.
• [29] Uncovering the mechanism of Naoxintong capsule against hypertension based on network analysis and in?vitro experiments. Chem Biol Drug Des. 2024 Jan;103(1):e14440. doi: 10.1111/cbdd.14440.
• [30] Disruption of adaptive energy metabolism and elevated ribosomal p-S6K1 levels contribute to INCL pathogenesis: partial rescue by resveratrol. Hum Mol Genet. 2011 Mar 15;20(6):1111-21. doi: 10.1093/hmg/ddq555. Epub 2010 Dec 28.
• [31] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [32] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [33] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [34] Sulforaphane induces differential modulation of mitochondrial biogenesis and dynamics in normal cells and tumor cells. Food Chem Toxicol. 2017 Feb;100:90-102. doi: 10.1016/j.fct.2016.12.020. Epub 2016 Dec 18.
• [35] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.