Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8F9BHW)

• DOT Name: MICOS complex subunit MIC25 (CHCHD6)
• Synonyms: Coiled-coil-helix cristae morphology protein 1; Coiled-coil-helix-coiled-coil-helix domain-containing protein 6
• Gene Name: CHCHD6
• Related Disease:
  Advanced cancer
  Non-alcoholic fatty liver disease
  Non-insulin dependent diabetes
  Tuberculosis
  Acute myelogenous leukaemia
• UniProt ID: MIC25_HUMAN
• Pfam ID: PF05300
• Sequence:
  MGSTESSEGRRVSFGVDEEERVRVLQGVRLSENVVNRMKEPSSPPPAPTSSTFGLQDGNL
  RAPHKESTLPRSGSSGGQQPSGMKEGVKRYEQEHAAIQDKLFQVAKREREAATKHSKASL
  PTGEGSISHEEQKSVRLARELESREAELRRRDTFYKEQLERIERKNAEMYKLSSEQFHEA
  ASKMESTIKPRRVEPVCSGLQAQILHCYRDRPHEVLLCSDLVKAYQRCVSAAHKG
• Function: Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane.
• Reactome Pathway: Cristae formation (R-HSA-8949613)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[3]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[4]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of MICOS complex subunit MIC25 (CHCHD6).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of MICOS complex subunit MIC25 (CHCHD6).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of MICOS complex subunit MIC25 (CHCHD6).	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of MICOS complex subunit MIC25 (CHCHD6).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of MICOS complex subunit MIC25 (CHCHD6).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of MICOS complex subunit MIC25 (CHCHD6).	[9]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of MICOS complex subunit MIC25 (CHCHD6).	[10]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of MICOS complex subunit MIC25 (CHCHD6).	[11]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of MICOS complex subunit MIC25 (CHCHD6).	[12]

References

• [1] CHCM1/CHCHD6, novel mitochondrial protein linked to regulation of mitofilin and mitochondrial cristae morphology.J Biol Chem. 2012 Mar 2;287(10):7411-26. doi: 10.1074/jbc.M111.277103. Epub 2012 Jan 6.
• [2] Integration of Multi-omics Data from Mouse Diversity Panel Highlights Mitochondrial Dysfunction in Non-alcoholic Fatty Liver Disease.Cell Syst. 2018 Jan 24;6(1):103-115.e7. doi: 10.1016/j.cels.2017.12.006. Epub 2018 Jan 18.
• [3] A genome-wide association study implicates that the TTC39C gene is associated with diabetic maculopathy with decreased visual acuity.Ophthalmic Genet. 2019 Jun;40(3):252-258. doi: 10.1080/13816810.2019.1633549. Epub 2019 Jul 2.
• [4] Secondary metabolites from Tetracera potatoria stem bark with anti-mycobacterial activity.J Ethnopharmacol. 2017 Jan 4;195:238-245. doi: 10.1016/j.jep.2016.11.027. Epub 2016 Nov 15.
• [5] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [6] 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.
• [7] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [8] Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks. Mutagenesis. 2014 Jan;29(1):17-26.
• [9] 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.
• [10] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [11] Peroxisome proliferator activated receptor gamma (PPAR-gama) ligand pioglitazone regulated gene networks in term human primary trophoblast cells. Reprod Toxicol. 2018 Oct;81:99-107.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] 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.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.