Affinage

ARMC1

Armadillo repeat-containing protein 1 · UniProt Q9NVT9

Round 2 corrected
Length
282 aa
Mass
31.3 kDa
Annotated
2026-04-28
79 papers in source corpus 7 papers cited in narrative 7 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARMC1 is a peripheral component of the mitochondrial contact site and cristae organizing system (MICOS)/mitochondrial intermembrane space bridging (MIB) complex that regulates mitochondrial distribution and dynamics. It localizes to both the cytosol and the outer mitochondrial membrane, where it partitions between two functionally opposing complexes: a MIRO-ARMC1-MTFR complex that antagonizes retrograde mitochondrial movement, and an ARMC1-DNAJC11 complex that facilitates ARMC1 release from mitochondria, with the balance between these interactions tuning steady-state mitochondrial positioning (PMID:31644573, PMID:40203102). Loss of ARMC1 causes mitochondrial fragmentation and perinuclear clustering without impairing cristae ultrastructure, respiration, or protein import (PMID:31644573), while ARMC1 overexpression shifts mitochondrial dynamics toward fusion by reducing DRP1 and stabilizing OPA1 and MFN2 (PMID:41153008).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2017 Low

    Pathway-level context for ARMC1 emerged from studies of SLC25A46, which showed that perturbation of MICOS-associated proteins alters mitochondrial morphology, implicating MICOS peripheral components in cristae and outer membrane organization.

    Evidence Co-IP of SLC25A46 with MICOS subunits and siRNA knockdown with mitochondrial morphology imaging

    PMID:28057766

    Open questions at the time
    • ARMC1 was implicated only by its MICOS membership, not directly studied
    • no direct interaction between ARMC1 and SLC25A46 was tested
    • mechanism linking MICOS periphery to morphology control was undefined
  2. 2019 High

    The first direct functional characterization established that ARMC1 is a dual-localization protein (cytosol and outer mitochondrial membrane) that associates with the MICOS/MIB complex and is required for normal mitochondrial distribution and motility, but not for cristae structure or respiration.

    Evidence Subcellular fractionation, co-immunoprecipitation, proximity ligation assay, siRNA knockdown with live-cell imaging of mitochondrial morphology and motility in human cells

    PMID:31644573

    Open questions at the time
    • mechanism by which ARMC1 loss causes fragmentation and reduced motility was unknown
    • identity of direct ARMC1 binding partners within the MICOS/MIB complex was not resolved
    • whether ARMC1's cytosolic pool has a distinct function was untested
  3. 2019 Medium

    Independent proximity labeling corroborated ARMC1's physical association with MIB complex components, strengthening its assignment as a bona fide MICOS/MIB-associated protein.

    Evidence BioID proximity-dependent biotinylation followed by mass spectrometry in human cells

    PMID:31617661

    Open questions at the time
    • proximity labeling does not distinguish direct from indirect interactions
    • stoichiometry and stability of ARMC1 within the MIB complex were not addressed
  4. 2021 Medium

    Inclusion of ARMC1 in the high-confidence human mitochondrial proteome (MitoCoP) confirmed its mitochondrial residence and indicated regulatory-range abundance and turnover dynamics.

    Evidence Quantitative mass spectrometry of enriched mitochondrial fractions with protein half-life measurements

    PMID:34800366

    Open questions at the time
    • no targeted functional analysis of ARMC1 was performed in this dataset
    • sub-mitochondrial compartmentalization was not resolved
  5. 2022 Medium

    Endogenous CRISPR tagging in living cells confirmed ARMC1's dual cytoplasmic and mitochondria-associated localization at physiological expression levels.

    Evidence CRISPR-mediated mEGFP knock-in with confocal live-cell imaging and AP-MS

    PMID:35271311

    Open questions at the time
    • dynamics of shuttling between cytosol and mitochondria were not captured
    • interactome from AP-MS was not functionally validated for ARMC1 specifically
  6. 2025 High

    The mechanistic basis of ARMC1's role in mitochondrial positioning was resolved: ARMC1 partitions between a MIRO-recruited complex that stabilizes MTFR and antagonizes retrograde transport, and a DNAJC11-mediated complex that releases ARMC1 from mitochondria; balanced shuttling between these states tunes mitochondrial distribution.

    Evidence AP-MS, reciprocal co-immunoprecipitation, CRISPR KO and overexpression with live-cell mitochondrial imaging, domain mapping and interaction-disrupting mutants, MTFR stability assays

    PMID:40203102

    Open questions at the time
    • structural basis of ARMC1's armadillo repeats engaging MIRO versus DNAJC11 is unresolved
    • whether ARMC1 shuttling is actively regulated by post-translational modifications is unknown
    • contribution of cytosolic ARMC1 pool beyond mitochondrial release is undefined
  7. 2025 Medium

    ARMC1 overexpression was shown to shift mitochondrial dynamics toward fusion by reducing DRP1 and stabilizing OPA1/MFN2, linking ARMC1 to the fission–fusion balance and oxidative stress suppression in a disease-relevant model of renal fibrosis.

    Evidence Lentiviral ARMC1 overexpression in tubular epithelial cells with western blotting for fission/fusion markers, ROS measurement, and in vivo cisplatin nephropathy model

    PMID:41153008

    Open questions at the time
    • direct physical interaction between ARMC1 and DRP1 or OPA1/MFN2 was not demonstrated
    • whether the pro-fusion effect reflects ARMC1's normal physiological role or a gain-of-function overexpression artifact is unclear
    • relevance to tissues beyond kidney epithelium is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the armadillo repeat domain of ARMC1 selectively engages its two distinct complexes (MIRO-MTFR versus DNAJC11), whether post-translational modifications regulate this partitioning, and whether ARMC1 directly contacts the fission/fusion machinery remain open questions.
  • no structural model of ARMC1 or its interfaces exists
  • regulation of ARMC1 mito-cytoplasmic shuttling is mechanistically uncharacterized
  • direct ARMC1 interaction with DRP1, OPA1, or MFN2 has not been tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2
Localization
GO:0005739 mitochondrion 4 GO:0005829 cytosol 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
DNAJC11MIRO1MIRO2MTFR1
Complex memberships
MICOS/MIB complex

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 ARMC1 (ArmC1) is a dual-localization protein found in both the cytosol and mitochondria, where it associates with the outer mitochondrial membrane via its carboxy-terminus and co-purifies with components of the mitochondrial contact site and cristae organizing system (MICOS)/mitochondrial intermembrane space bridging (MIB) complex. Its levels are reduced upon MICOS/MIB complex depletion. Loss of ArmC1 results in mitochondrial fragmentation and reduced mitochondrial motility, but no defects in cristae ultrastructure, respiration, or protein import, identifying it as a peripheral MICOS/MIB component required for mitochondrial distribution. Subcellular fractionation, co-immunoprecipitation, immunofluorescence microscopy, siRNA knockdown with live-cell imaging of mitochondrial morphology and motility, proximity ligation assay PloS one High 31644573
2025 ARMC1 partitions between two distinct mitochondrial protein complexes that have opposing effects on mitochondrial distribution. In one complex, the mitochondrial trafficking adaptor MIRO recruits ARMC1, which in turn mediates the assembly and stability of the mitochondrial fission regulator MTFR; MIRO-MTFR complexes specifically antagonize retrograde mitochondrial movement. In a second complex, the MIB/MICOS subunit DNAJC11 facilitates ARMC1 release from mitochondria, limiting mitochondrially localized ARMC1 abundance. ARMC1 deletion causes perinuclear mitochondrial clustering that is not rescued by disrupting MIRO-MTFR assembly alone, whereas disrupting the ARMC1-DNAJC11 interaction leads to excessive mitochondrial ARMC1 and distinct mitochondrial defects, demonstrating that balanced mito-cytoplasmic shuttling of ARMC1 tunes steady-state mitochondrial distribution. AP-MS to identify complex members, co-immunoprecipitation to validate MIRO-ARMC1-MTFR and ARMC1-DNAJC11 interactions, CRISPR knockout and overexpression with live-cell mitochondrial imaging, domain mapping and interaction-disrupting mutants, MTFR stability assays Science advances High 40203102
2025 Mesenchymal stem cell (MSC)-conditioned medium increases ARMC1 protein levels in TGF-β1-treated tubular epithelial cells. ARMC1 overexpression reduces DRP1 (a pro-fission GTPase), enhances OPA1 and MFN2 (pro-fusion proteins), lowers reactive oxygen species, and suppresses fibrosis markers (α-SMA, fibronectin, collagen-I), indicating that ARMC1 shifts mitochondrial dynamics toward fusion and reduces oxidative stress in the context of renal fibrosis. Proteomics of renal tissue (adenine nephropathy model), lentiviral ARMC1 overexpression in HK-2 cells, western blotting for DRP1/OPA1/MFN2/NRF2/SOD1/SOD2, ROS measurement, mitochondrial morphology assessment, cisplatin mouse model with MSC intervention Stem cell research & therapy Medium 41153008
2021 ARMC1 is catalogued as a component of the human mitochondrial high-confidence proteome (MitoCoP), placing it among >1,100 proteins with validated mitochondrial localization, with abundance and turnover dynamics consistent with a regulatory rather than structural role. Quantitative mass spectrometry of enriched mitochondrial fractions from human cells, protein half-life measurements Cell metabolism Medium 34800366
2022 Endogenous tagging (OpenCell) of ARMC1 by CRISPR-mediated fluorescent knock-in reveals cytoplasmic and mitochondria-associated localization in living human cells, consistent with its dual compartmentalization. CRISPR endogenous tagging with mEGFP, confocal live-cell imaging, AP-MS for interaction partners Science (New York, N.Y.) Medium 35271311
2019 BioID proximity labeling of mitochondrial intermembrane space proteases places ARMC1 in proximity to MIB complex components, corroborating its association with this multi-subunit cristae-organizing assembly. In vivo proximity-dependent biotinylation (BioID) followed by mass spectrometry Proteomics Medium 31617661
2017 SLC25A46, a protein that interacts with the MICOS complex (which includes ARMC1 as a component), shows that perturbation of MICOS-associated proteins leads to mitochondrial hyperfusion, providing pathway-level context for ARMC1's role in cristae/outer membrane organization. Co-immunoprecipitation of SLC25A46 with MICOS subunits, siRNA knockdown, mitochondrial morphology imaging Molecular biology of the cell Low 28057766

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1998 Characterization of Sfp, a Bacillus subtilis phosphopantetheinyl transferase for peptidyl carrier protein domains in peptide synthetases. Biochemistry 583 9484229
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell 423 26871637
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1998 Identification of a Mycobacterium tuberculosis gene cluster encoding the biosynthetic enzymes for assembly of the virulence-conferring siderophore mycobactin. Chemistry & biology 366 9831524
2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PloS one 312 23251661
2021 Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context. Cell metabolism 239 34800366
2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes. Genomics 222 17207965
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
1997 Enterobactin biosynthesis in Escherichia coli: isochorismate lyase (EntB) is a bifunctional enzyme that is phosphopantetheinylated by EntD and then acylated by EntE using ATP and 2,3-dihydroxybenzoate. Biochemistry 193 9214294
2011 Pancreas divisum is not a cause of pancreatitis by itself but acts as a partner of genetic mutations. The American journal of gastroenterology 156 22158025
2009 Ubiquitin-mediated proteolysis of HuR by heat shock. The EMBO journal 142 19322201
2005 Scanning the human proteome for calmodulin-binding proteins. Proceedings of the National Academy of Sciences of the United States of America 139 15840729
2011 Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein. The Journal of biological chemistry 131 21832049
1998 The nonribosomal peptide synthetase HMWP2 forms a thiazoline ring during biogenesis of yersiniabactin, an iron-chelating virulence factor of Yersinia pestis. Biochemistry 129 9709002
2017 An Interaction Landscape of Ubiquitin Signaling. Molecular cell 119 28190767
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2000 Vibriobactin biosynthesis in Vibrio cholerae: VibH is an amide synthase homologous to nonribosomal peptide synthetase condensation domains. Biochemistry 98 11112537
2021 Environmental Clonal Spread of Azole-Resistant Candida parapsilosis with Erg11-Y132F Mutation Causing a Large Candidemia Outbreak in a Brazilian Cancer Referral Center. Journal of fungi (Basel, Switzerland) 81 33808442
2007 A mechanism-based aryl carrier protein/thiolation domain affinity probe. Journal of the American Chemical Society 72 17469819
2017 Rapid degradation of mutant SLC25A46 by the ubiquitin-proteasome system results in MFN1/2-mediated hyperfusion of mitochondria. Molecular biology of the cell 68 28057766
1990 Immunoelectron microscopic localization of amyloid beta protein in the diffuse plaques of Alzheimer-type dementia. Brain research 68 2407313
2022 Scalable multiplex co-fractionation/mass spectrometry platform for accelerated protein interactome discovery. Nature communications 65 35831314
2021 Comprehensive interactome profiling of the human Hsp70 network highlights functional differentiation of J domains. Molecular cell 64 33957083
2019 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. Nature communications 60 31515488
2018 Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy. Proceedings of the National Academy of Sciences of the United States of America 59 29987050
2006 A protein interaction surface in nonribosomal peptide synthesis mapped by combinatorial mutagenesis and selection. Proceedings of the National Academy of Sciences of the United States of America 59 16567620
2000 Expression, purification, and characterization of HMWP2, a 229 kDa, six domain protein subunit of Yersiniabactin synthetase. Biochemistry 58 10769129
2012 The Arabidopsis ARCP protein, CSI1, which is required for microtubule stability, is necessary for root and anther development. The Plant cell 46 22427339
2019 PLEKHA4/kramer Attenuates Dishevelled Ubiquitination to Modulate Wnt and Planar Cell Polarity Signaling. Cell reports 42 31091453
1999 Tandem heterocyclization activity of the multidomain 230 kDa HMWP2 subunit of Yersinia pestis yersiniabactin synthetase: interaction of the 1-1382 and 1383-2035 fragments. Biochemistry 42 10529249
2006 Localized protein interaction surfaces on the EntB carrier protein revealed by combinatorial mutagenesis and selection. Journal of the American Chemical Society 41 16925399
2010 Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. PloS one 37 20877624
2001 The mtaA gene of the myxothiazol biosynthetic gene cluster from Stigmatella aurantiaca DW4/3-1 encodes a phosphopantetheinyl transferase that activates polyketide synthases and polypeptide synthetases. Journal of biochemistry 37 11134965
2007 The hotdog thioesterase EntH (YbdB) plays a role in vivo in optimal enterobactin biosynthesis by interacting with the ArCP domain of EntB. Journal of bacteriology 33 17675380
2010 Kinetic and inhibition studies of dihydroxybenzoate-AMP ligase from Escherichia coli. Biochemistry 31 20359185
2021 Single cell RNA-seq reveals genes vital to in vitro fertilized embryos and parthenotes in pigs. Scientific reports 29 34257377
2001 Yersiniabactin synthetase: probing the recognition of carrier protein domains by the catalytic heterocyclization domains, Cy1 and Cy2, in the chain-initiating HWMP2 subunit. Biochemistry 29 11318656
2004 Kinetic and regiospecific interrogation of covalent intermediates in the nonribosomal peptide synthesis of yersiniabactin. Journal of the American Chemical Society 26 15479080
2023 TRIM67 drives tumorigenesis in oligodendrogliomas through Rho GTPase-dependent membrane blebbing. Neuro-oncology 25 36215168
2021 ARMC Subfamily: Structures, Functions, Evolutions, Interactions, and Diseases. Frontiers in molecular biosciences 25 34912852
2019 Global Interactome Mapping of Mitochondrial Intermembrane Space Proteases Identifies a Novel Function for HTRA2. Proteomics 24 31617661
2002 Carrier protein recognition in siderophore-producing nonribosomal peptide synthetases. Biochemistry 24 12081492
2023 Genome-Wide Association Study to Identify QTL for Carcass Traits in Korean Hanwoo Cattle. Animals : an open access journal from MDPI 21 37685003
2019 Armadillo repeat-containing protein 1 is a dual localization protein associated with mitochondrial intermembrane space bridging complex. PloS one 21 31644573
2019 Natural Variation in a Dendritic Scaffold Protein Remodels Experience-Dependent Plasticity by Altering Neuropeptide Expression. Neuron 17 31757604
2021 Single-cell RNA-seq reveals mRNAs and lncRNAs important for oocytes in vitro matured in pigs. Reproduction in domestic animals = Zuchthygiene 15 33496347
2004 Gene cloning, expression and functional characterization of a phosphopantetheinyl transferase from Vibrio anguillarum serotype O1. Archives of microbiology 14 15551118
2016 Intracellular co-localization of the Escherichia coli enterobactin biosynthetic enzymes EntA, EntB, and EntE. Biochemical and biophysical research communications 13 27470582
2001 Nonribosomal biosynthesis of microbial chromopeptides. Progress in nucleic acid research and molecular biology 13 11642364
2022 Evidence of an intracellular interaction between the Escherichia coli enzymes EntC and EntB and identification of a potential electrostatic channeling surface. Biochimie 10 35952947
2005 Chemoenzymatic approaches for streamlined detection of active site modifications on thiotemplate assembly lines using mass spectrometry. Biochemistry 8 16245932
2024 Genome-Wide Association Study for Milk Somatic Cell Score in Holstein Friesian Cows in Slovenia. Animals : an open access journal from MDPI 7 39335302
2005 Thioesterase portability and peptidyl carrier protein swapping in yersiniabactin synthetase from Yersinia pestis. Biochemistry 7 15779920
2017 Visualizing the Adenylation Activities and Protein-Protein Interactions of Aryl Acid Adenylating Enzymes. Chembiochem : a European journal of chemical biology 6 28871667
2011 Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrio anguillarum strain 775. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine 6 21286786
2024 Heat Stress Inhibits Pollen Development by Degrading mRNA Capping Enzyme ARCP1 and ARCP2. Plant, cell & environment 5 39373148
2022 Pan-cancer analyses of Jab1/COPS5 reveal oncogenic role and clinical outcome in human cancer. Heliyon 5 36643321
2025 ARMC1 partitions between distinct complexes and assembles MIRO with MTFR to control mitochondrial distribution. Science advances 4 40203102
2022 The Valuable Role of ARMC1 in Invasive Breast Cancer as a Novel Biomarker. BioMed research international 3 35378785
2022 Selection of a stable reference gene for relative copy number profiling of porcine chromosomal genes using SYBR green qPCR. Animal biotechnology 2 35767335
2018 Challenges of Connecting Chemistry to Pharmacology: Perspectives from Curating the IUPHAR/BPS Guide to PHARMACOLOGY. ACS omega 2 30087946
2025 The enterobactin biosynthetic intermediate 2,3-dihydroxybenzoic acid is a competitive inhibitor of the Escherichia coli isochorismatase EntB. Protein science : a publication of the Protein Society 1 40400396
2021 Analgesic refractory colic pain: Is prolonged conservative management appropriate? The American journal of emergency medicine 1 33618037
2026 Study on biomarkers of homocysteine-induced transformation of vascular smooth muscle cells into foam cells. Scientific reports 0 41644998
2026 Transdiagnostic functional connectome signature of anhedonia relates to neurotransmitter and genetic profiles. Journal of affective disorders 0 41864356
2025 Functional and structural characterization of Stenotrophomonas maltophilia EntB, an unusual form of isochorismatase for siderophore synthesis. Acta crystallographica. Section F, Structural biology communications 0 40464617
2025 Multi-Omic Analysis Identifies Key Genes Driving Testicular Fusion in Spodoptera litura. International journal of molecular sciences 0 40565028
2025 Mesenchymal stem cells inhibit mitochondrial fission by upregulating armadillo repeat containing 1, ameliorating oxidative stress in renal fibrosis. Stem cell research & therapy 0 41153008
2025 Discriminating childhood traumatic experiences by molecular profiles: the case of neglect and sexual abuse. European journal of psychotraumatology 0 41195746