Affinage

DNAJC11

DnaJ homolog subfamily C member 11 · UniProt Q9NVH1

Length
559 aa
Mass
63.3 kDa
Annotated
2026-04-28
14 papers in source corpus 5 papers cited in narrative 6 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DNAJC11 is a mitochondrial outer membrane J-domain protein that maintains mitochondrial cristae architecture and regulates mitochondrial distribution. It assembles into a high-molecular-weight supercomplex with MICOS components (mitofilin, CHCHD3, CHCHD6), SAM50, metaxins, and VDACs, where its DUF3395 domain mediates protein–protein interactions and its J-domain directs mitochondrial localization; its stability depends on mitofilin and SAM50 (PMID:17624330, PMID:25111180, PMID:31550165). Loss of DNAJC11 in mice causes motor neuron vacuolation with disorganized inner membrane cristae and lymphoid abnormalities, a phenotype rescued by human DNAJC11 overexpression (PMID:25111180). DNAJC11 also regulates ARMC1 release from mitochondria to tune mitochondrial distribution (PMID:40203102) and can stabilize SARS-CoV-2 NSP3 to promote double-membrane vesicle formation during viral replication (PMID:40872740).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2007 Medium

    Identification of DNAJC11 as a component of a mitofilin-containing mitochondrial complex with SAM50, metaxins, and CHCHD proteins established that DNAJC11 participates in a multi-subunit assembly at the mitochondrial membranes, raising the question of its specific contribution.

    Evidence Immunocapture with mitofilin monoclonal antibody followed by protein identification from mitochondrial extracts

    PMID:17624330

    Open questions at the time
    • Single immunocapture study without reciprocal pull-down from DNAJC11 side
    • No functional consequence of DNAJC11 loss was tested
    • Topology and submitochondrial localization of DNAJC11 were undefined
  2. 2014 High

    Determination that DNAJC11 localizes to the mitochondrial outer membrane periphery, depends on mitofilin/SAM50 for stability, and is essential for cristae organization in motor neurons resolved its functional role: DNAJC11 is required for inner membrane architecture, and its loss causes neuronal vacuolation from cristae disorganization.

    Evidence Subcellular fractionation, immunofluorescence, siRNA knockdown of mitofilin/SAM50 in HeLa cells; ENU mutagenesis in mice with EM neuropathology and genetic rescue by human DNAJC11 overexpression

    PMID:25111180

    Open questions at the time
    • Molecular mechanism by which DNAJC11 maintains cristae structure was not defined
    • Whether the J-domain chaperone activity is enzymatically required was untested
    • The human disease relevance of DNAJC11 loss-of-function was not established
  3. 2019 High

    Systematic interactome mapping and domain dissection revealed that the DUF3395 domain mediates DNAJC11 protein–protein interactions (including MICOS, VDACs, ribosomes, Hsp70) while the J-domain determines mitochondrial targeting, defining the modular logic of DNAJC11 function.

    Evidence AP-MS of DNAJC11-FLAG in HEK293FT cells and transgenic mouse cerebrum; domain deletion and mutation analysis

    PMID:31550165

    Open questions at the time
    • Whether Hsp70 binding reflects active chaperone cycling or passive scaffolding is unknown
    • Functional significance of ribosomal and synaptic protein interactions was not tested
    • No structural model of DNAJC11 within the MICOS/MIB supercomplex exists
  4. 2025 Medium

    Discovery that DNAJC11 facilitates ARMC1 release from mitochondria to control mitochondrial distribution expanded its role beyond cristae maintenance to a regulator of organelle positioning.

    Evidence Co-IP, genetic perturbation of ARMC1–DNAJC11 interaction, live-cell imaging of mitochondrial distribution

    PMID:40203102

    Open questions at the time
    • Single study; independent replication is needed
    • Mechanism by which DNAJC11 releases ARMC1 (chaperone activity vs. competitive binding) is undefined
    • Relationship between ARMC1-dependent distribution and cristae organization is unexplored
  5. 2025 Medium

    DNAJC11 was shown to stabilize SARS-CoV-2 NSP3 and promote NSP3–NSP4 interaction for double-membrane vesicle biogenesis, revealing that its chaperone-like activity can be co-opted during viral infection.

    Evidence MS-based interaction identification, Co-IP, siRNA knockdown and overexpression of DNAJC11, EM quantification of DMVs

    PMID:40872740

    Open questions at the time
    • Single study on one viral system; breadth of host–pathogen relevance is unknown
    • Whether J-domain-dependent Hsp70 cycling is required for NSP3 stabilization is untested
    • Impact on viral replication titers was not reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • The catalytic contribution of DNAJC11's J-domain chaperone cycle (Hsp70 co-chaperone activity) versus its scaffolding function within the MICOS/MIB supercomplex remains mechanistically unresolved, and no human Mendelian disease has been linked to DNAJC11 mutations.
  • No reconstitution of DNAJC11 J-domain stimulated ATPase activity with Hsp70 has been performed
  • No structural data for DNAJC11 or its complexes exist
  • Human genetic loss-of-function consequences are uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005739 mitochondrion 2
Pathway
R-HSA-1852241 Organelle biogenesis and maintenance 3
Partners
ARMC1CHCHD3CHCHD6IMMTMTX1MTX2SAMM50
Complex memberships
MICOS/MIB supercomplex

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 DNAJC11 exists as part of a mitochondrial complex with mitofilin (inner membrane protein), SAM50, metaxins 1 and 2, CHCHD3, and CHCHD6, immunocaptured by a mitofilin monoclonal antibody, suggesting a role in protein import or maintenance of mitochondrial structure. Immunoprecipitation (monoclonal antibody immunocapture) followed by protein identification FEBS letters Medium 17624330
2014 DNAJC11 localizes to the periphery of the mitochondrial outer membrane (full-length 63 kDa isoform), with putative additional isoforms showing differential submitochondrial localization; it is assembled in a high molecular weight complex similarly to mitofilin; downregulation of mitofilin or SAM50 reduces DNAJC11 protein levels, indicating DNAJC11 stability depends on MICOS complex members. Subcellular fractionation, immunofluorescence, western blotting after siRNA knockdown of mitofilin and SAM50 in HeLa cells; rescue experiments with human DNAJC11 overexpression in mutant mice PloS one High 25111180
2014 Loss-of-function (splice-site hypomorphic mutation) of DNAJC11 in mice causes motor neuron vacuolation arising from mitochondria with disorganized inner membrane cristae, as well as lymphoid abnormalities, establishing DNAJC11 as required for mitochondrial inner membrane organization in neurons. ENU forward genetics screen, neuropathological analysis (electron microscopy of motor neurons), genetic rescue with human DNAJC11 overexpression PloS one High 25111180
2019 DNAJC11 interacts with MICOS complex members (confirming cristae organization role), VDACs at the outer mitochondrial membrane, ribosomal subunits and Hsp70 chaperones in metabolically active cells (HEK293FT), and synaptic proteins in mouse cerebrum; the DUF3395 domain mediates protein-protein interactions while the J-domain determines mitochondrial localization. Affinity purification–mass spectrometry (DNAJC11-FLAG immunoprecipitation) in HEK293FT cells and transgenic mice; domain deletion/mutation analysis Journal of proteome research High 31550165
2025 DNAJC11 facilitates ARMC1 release from mitochondria; disrupting the ARMC1–DNAJC11 interaction leads to excessive mitochondrially localized ARMC1 and distinct mitochondrial distribution defects, placing DNAJC11 as a regulator of ARMC1 mito-cytoplasmic shuttling that tunes steady-state mitochondrial distribution. Co-immunoprecipitation, genetic perturbation (ARMC1 deletion, disruption of DNAJC11–ARMC1 interaction), live-cell imaging of mitochondrial distribution Science advances Medium 40203102
2025 DNAJC11 interacts with SARS-CoV-2 NSP3, stabilizes NSP3 protein through endogenous apoptosis pathways, and facilitates NSP3–NSP4 interaction, thereby promoting double-membrane vesicle (DMV) formation required for viral replication; DNAJC11 knockdown reduces DMV number and size, while DNAJC11 supplementation restores them. Mass spectrometry identification of interaction, co-immunoprecipitation, siRNA knockdown, ectopic overexpression, electron microscopy of DMVs Viruses Medium 40872740

Source papers

Stage 0 corpus · 14 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The mitochondrial inner membrane protein mitofilin exists as a complex with SAM50, metaxins 1 and 2, coiled-coil-helix coiled-coil-helix domain-containing protein 3 and 6 and DnaJC11. FEBS letters 179 17624330
2015 Evolution and structural organization of the mitochondrial contact site (MICOS) complex and the mitochondrial intermembrane space bridging (MIB) complex. Biochimica et biophysica acta 159 26477565
2017 Genome-wide identification of genes essential for podocyte cytoskeletons based on single-cell RNA sequencing. Kidney international 69 28709640
2003 Identification and characterization of FLJ10737 and CAMTA1 genes on the commonly deleted region of neuroblastoma at human chromosome 1p36.31-p36.23. International journal of oncology 62 12964007
2006 Reduced expression of CAMTA1 correlates with adverse outcome in neuroblastoma patients. Clinical cancer research : an official journal of the American Association for Cancer Research 53 16397034
2014 A splicing mutation in the novel mitochondrial protein DNAJC11 causes motor neuron pathology associated with cristae disorganization, and lymphoid abnormalities in mice. PloS one 42 25111180
2015 The evolution of MICOS: Ancestral and derived functions and interactions. Communicative & integrative biology 29 27065250
2019 Mapping Interactome Networks of DNAJC11, a Novel Mitochondrial Protein Causing Neuromuscular Pathology in Mice. Journal of proteome research 12 31550165
2007 Allelic variants of CAMTA1 and FLJ10737 within a commonly deleted region at 1p36 in neuroblastoma. European journal of cancer (Oxford, England : 1990) 10 17222547
2016 Down-regulation of HSP40 gene family following OCT4B1 suppression in human tumor cell lines. Iranian journal of basic medical sciences 8 27081464
2025 ARMC1 partitions between distinct complexes and assembles MIRO with MTFR to control mitochondrial distribution. Science advances 4 40203102
2026 Human lncRNA RMRP interacts with DEAD-box helicases and modulates mitochondrial function. Proceedings of the National Academy of Sciences of the United States of America 1 41719330
2026 The genetic associations of DNAJC family members with Parkinson's disease: comprehensive evidence from burden analysis and Mendelian randomization. Human genetics 0 41951985
2025 DNAJ Homolog Subfamily C Member 11 Stabilizes SARS-CoV-2 NSP3 to Promote Double-Membrane Vesicle Formation. Viruses 0 40872740