Affinage

TIMM44

Mitochondrial import inner membrane translocase subunit TIM44 · UniProt O43615

Length
452 aa
Mass
51.4 kDa
Annotated
2026-06-10
30 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TIMM44 (Tim44) is the central scaffold of the presequence translocase-associated import motor (PAM), coupling mtHsp70 ATPase cycling to the vectorial translocation and unfolding of preproteins entering the mitochondrial matrix (PMID:8654364, PMID:9687491). It is a peripheral inner-membrane protein localized to the inner membrane and cristae, imported in a membrane-potential-dependent manner and proteolytically matured, with a topology that exposes its C-terminal Cys-369 to the intermembrane space (PMID:9419343, PMID:12054602). Its stably folded C-terminal domain adopts an NTF2-like fold and anchors the motor both to the TIM23 channel—contacting the matrix-exposed loop of Tim23 and binding Tim17—and to cardiolipin-containing membrane lipids through amphipathic N-terminal helices A1/A2 that act as a membrane sensor (PMID:18084070, PMID:19863062, PMID:21342097, PMID:28440746). The intrinsically disordered N-terminal domain functions as a dynamic arm that tethers mtHsp70 (Ssc1) to the translocation site and binds incoming presequences (PMID:18426906, PMID:28440746). Tim44 contacts both the ATPase and peptide-binding domains of mtHsp70 in a nucleotide-regulated manner: ATP promotes complex formation, hydrolysis occurs within the complex, the nucleotide exchange factor Mge1p drives ADP-form mtHsp70 release, and substrate binding to mtHsp70 triggers dissociation of the complex from Tim44, providing a regulated release step that drives translocation (PMID:8918457, PMID:15489862, PMID:10913171). Tim44 is dispensable for the number of translocation contact sites but specifically required for pulling tightly folded domains across the membrane and for recruiting mtHsp70 to translocating substrates to ensure their proper folding (PMID:9312000, PMID:9687491, PMID:10824101), and it differentially recruits the Pam18/Pam16 J-complex to the TIM23 translocase (PMID:18400944). In mammalian cells TIMM44 supports import of antioxidant enzymes including SOD2, and its loss elevates ROS to engage downstream stress signaling (PMID:16186389, PMID:27849558).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1996 High

    Established that the mtHsp70–Tim44 complex performs two mechanistically distinct import tasks, defining when a motor interaction is actually needed.

    Evidence Yeast Ssc1 mutant analysis with in organello import of folded vs loosely folded substrates

    PMID:8654364

    Open questions at the time
    • Did not define the nucleotide-state geometry of the interaction
    • Substrate-folding threshold for requiring the complex not quantified
  2. 1996 High

    Defined the nucleotide-driven reaction cycle, showing how ATP binding, hydrolysis, and Mge1p-driven exchange sequence the formation and dissolution of the mtHsp70–Tim44 complex.

    Evidence Biochemical reconstitution and nucleotide-dependent co-precipitation with Mge1p depletion in yeast

    PMID:8918457

    Open questions at the time
    • Did not localize the mtHsp70 domains contacting Tim44
    • Coupling to mechanical force generation not directly measured
  3. 1997 High

    Clarified the architecture of the import machinery, distinguishing the stable Tim23/Tim17 core channel from the substoichiometric mtHsp70–Tim44 motor.

    Evidence Blue native electrophoresis and co-immunoprecipitation of assembled mitochondrial complexes

    PMID:9312000

    Open questions at the time
    • Dynamic stoichiometry during active translocation unresolved
    • Spatial coupling of motor to channel not structurally defined
  4. 1998 High

    Characterized mammalian Tim44 localization, import, and membrane association, extending the yeast model to mammals.

    Evidence Immunofluorescence, immunoEM, import and Na2CO3 extraction assays in COS7/mitochondria

    PMID:9419343

    Open questions at the time
    • Mammalian motor partners not mapped here
    • Functional reconstitution of mammalian PAM not performed
  5. 1998 High

    Demonstrated that Tim44 is not a structural channel component but is specifically required to pull and unfold tightly folded domains, isolating its motor-specific role.

    Evidence Conditional yeast tim44 mutant with quantitative import assays and EM of import sites

    PMID:9687491

    Open questions at the time
    • Mechanical force transmission mechanism not defined
    • Did not separate scaffolding vs motor-coupling contributions
  6. 1999 High

    Showed Tim44 is an elongated monomer with a folded C-terminal domain that binds cardiolipin-containing membranes, establishing its lipid-anchoring property.

    Evidence Limited proteolysis, ultracentrifugation, and liposome/monolayer binding with recombinant Tim44

    PMID:10430866

    Open questions at the time
    • Specific lipid-binding residues not yet mapped
    • Membrane topology relative to the channel not resolved
  7. 1999 High

    Identified an essential 18-residue J-related segment required for productive, ATP-regulated mtHsp70 binding and unfolding activity.

    Evidence Deletion mutagenesis, in organello import, and co-precipitation in yeast

    PMID:10352014

    Open questions at the time
    • Structural basis of segment–Hsp70 contact unknown
    • Relationship to J-complex recruitment not addressed here
  8. 2000 High

    Mapped the primary Tim44 contact to the ATPase domain of mtHsp70 in an ATP-sensitive manner, separating the Tim44-binding site from the substrate-binding site.

    Evidence Yeast two-hybrid and co-precipitation of truncated mtHsp70 imported into mitochondria

    PMID:10913171

    Open questions at the time
    • Did not explain peptide-binding-domain enhancement at residue level
    • Interdomain communication mechanism not yet defined
  9. 2000 Medium

    Linked Tim44 to recruitment of mtHsp70 onto translocating substrates and to proper folding of imported proteins, showing the motor's downstream role in matrix proteostasis.

    Evidence Conditional tim44 mutant with co-IP of mtHsp70 with substrates and in organello folding assays

    PMID:10824101

    Open questions at the time
    • Single lab, limited substrate set
    • Did not distinguish direct vs indirect folding effects
  10. 2001 High

    Refined the mtHsp70 binding interface to the peptide-binding domain beta-core and showed interdomain helices transmit nucleotide state to coordinate substrate-triggered release.

    Evidence Chimeric mtHsp70/DnaK proteins in yeast mitochondria with co-precipitation and import assays

    PMID:11733493

    Open questions at the time
    • Atomic structure of the interface not resolved
    • Quantitative coupling of release to translocation rate not measured
  11. 2002 Medium

    Established Tim44 membrane topology by showing Cys-369 of the C-terminal domain is exposed to the intermembrane space.

    Evidence Membrane-impermeable biotin maleimide labeling of intact mitochondria with immunoprecipitation

    PMID:12054602

    Open questions at the time
    • Single residue, single method topology
    • Topology of N-terminal domain not addressed
  12. 2002 Medium

    Showed the mtHsp70 peptide-binding domain regulates Tim44 binding through interdomain communication, with paralogous Hsp70s exerting negative effects.

    Evidence Chimeric Hsp70 proteins with co-precipitation and in vivo complementation in yeast

    PMID:12032075

    Open questions at the time
    • Single lab
    • Physiological role of paralog specificity not established
  13. 2004 High

    Demonstrated that substrate binding to mtHsp70 disrupts the Tim44–mtHsp70 interaction via concerted two-domain conformational changes, defining the regulated release switch.

    Evidence In vitro binding with mtHsp70 domain mutants plus in vivo complementation

    PMID:15489862

    Open questions at the time
    • Real-time kinetics of release not measured
    • Structure of the substrate-bound transition state unknown
  14. 2005 Medium

    Connected mammalian Tim44 to import of antioxidant enzymes and to mitochondrial redox/energetic homeostasis under metabolic stress.

    Evidence siRNA and overexpression in human aortic smooth muscle cells with ROS, ATP, and membrane potential assays

    PMID:16186389

    Open questions at the time
    • Direct import of named enzymes not biochemically tracked
    • Single cell type and single lab
  15. 2007 High

    Provided the first atomic structure of human Tim44 C-terminal domain, revealing an NTF2-like fold and a lipid-binding cavity with conformational responsiveness to lipid.

    Evidence X-ray crystallography at 1.9 Å with pentaethylene glycol-bound form

    PMID:18084070

    Open questions at the time
    • N-terminal domain not crystallized
    • Lipid binding in the membrane context not directly shown
  16. 2008 High

    Revealed that Tim44 differentially recruits PAM modules—supporting J-complex association while a Tim44-independent Pam17–Tim23 contact exists.

    Evidence Conditional tim44-804 mutant with reciprocal co-immunoprecipitation of TIM23 complexes

    PMID:18400944

    Open questions at the time
    • Mechanism of J-complex recruitment by Tim44 not defined
    • Order of module assembly not established
  17. 2008 High

    Localized the mtHsp70-interaction and substrate-release functions to the N-terminal 167 residues, with a 30-residue region governing both release and translocon contact.

    Evidence N-terminal truncation and alanine scanning with in vitro binding and in vivo complementation

    PMID:18426906

    Open questions at the time
    • Disordered NTD conformation during cycling not resolved
    • Direct presequence contacts not yet mapped here
  18. 2009 Medium

    Identified helix A1 (and A2) of the C-terminal domain as the cardiolipin-binding membrane attachment element.

    Evidence Truncation mutants with liposome binding assays and molecular dynamics in yeast Tim44

    PMID:19863062

    Open questions at the time
    • MD-based lipid interactions not biochemically corroborated at residue level
    • Single lab
  19. 2009 Medium

    Placed Tim44 at a later translocation step than Pam17, defining temporal order within the PAM motor via genetic cooperation.

    Evidence Genetic synthetic interaction analysis with in organello import assays

    PMID:19577659

    Open questions at the time
    • Molecular basis of the temporal split not defined
    • Single lab genetic study
  20. 2011 Medium

    Defined amphipathic helices A1/A2 as a switchable membrane sensor that anchors the PAM complex to TIM23.

    Evidence X-ray crystallography of Tim44-CTD with biochemical membrane binding assays

    PMID:21342097

    Open questions at the time
    • Limited functional validation in vivo
    • Conformational switch not captured in the membrane state
  21. 2016 Medium

    Connected TIMM44 to cancer cell survival via an SOD2–ROS–Akt–mTOR axis exploited by a mitochondria-targeting drug.

    Evidence siRNA, RNA-seq, mass spectrometry, and IR-58 treatment in colorectal cancer cells and xenografts

    PMID:27849558

    Open questions at the time
    • Whether the effect is purely through SOD2 import unresolved
    • Single lab
  22. 2017 High

    Resolved the architecture of Tim44 within the translocon: a disordered NTD acting as a dynamic arm binding presequence and Hsp70, and a CTD anchoring to Tim23 and Tim17.

    Evidence Site-specific in vivo crosslinking, genetics, and in vitro NTD binding in S. cerevisiae

    PMID:28440746

    Open questions at the time
    • Atomic structure of NTD–channel contacts lacking
    • Dynamics during a translocation cycle not visualized
  23. 2017 Medium

    Demonstrated a druggable pocket in the Tim44 CTD required for binding both translocating precursor and mtHsp70, validating Tim44 as a chemical target.

    Evidence Genetic screen, mutagenesis, docking/MD, and biochemical import assays with MB-10

    PMID:28167535

    Open questions at the time
    • Co-structure with inhibitor not solved
    • Selectivity over other NTF2-fold proteins not established
  24. 2020 Medium

    Showed TIMM44 mRNA is post-transcriptionally stabilized by HuR, linking its expression to cancer cell proliferation.

    Evidence Luciferase reporter with TIMM44 3'UTR, HuR perturbation and TIMM44 siRNA in ovarian cancer lines

    PMID:32901414

    Open questions at the time
    • Mechanism downstream of TIMM44 in this context not defined
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the disordered NTD and lipid-anchored CTD coordinate motor cycling in a near-atomic, dynamic model of the active human PAM–TIM23 supercomplex remains unresolved.
  • No structure of the assembled, substrate-engaged human motor
  • Temporal coupling of NTD presequence binding to mtHsp70 cycling not directly visualized
  • Mechanistic basis of disease-associated CTD mutations (e.g. P308Q) not functionally dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0060090 molecular adaptor activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-392499 Metabolism of proteins 3 R-HSA-9609507 Protein localization 3
Partners
HURMGE1PAM16PAM17PAM18SSC1/MTHSP70TIM17TIM23
Complex memberships
PAM (presequence translocase-associated import motor)TIM23 translocase

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Tim44 and mtHsp70 form a complex at the matrix face of the inner membrane import site; the Tim core complex (~90K, containing Tim23 and Tim17) can stably interact with preproteins and determines the number of translocation contact sites, while mtHsp70 and Tim44 are not stoichiometric components of the 600K supercomplex spanning both membranes. Blue native electrophoresis, co-immunoprecipitation of assembled complexes The EMBO journal High 9312000
1996 The mtHsp70–Tim44 complex drives two distinct steps: (1) import of loosely folded preproteins does not require a detectable Hsp70–Tim44 complex, whereas (2) unfolding and import of tightly folded preproteins requires a reversible, nucleotide-dependent interaction between mtHsp70 and Tim44 involving ATPase-domain conformational change. Yeast mtHsp70 mutant analysis (Ssc1-2p and Ssc1-3p'), in organello import assays with folded and loosely folded substrates The EMBO journal High 8654364
1996 The nucleotide exchange factor Mge1p (MGE) drives the ATP-dependent reaction cycle of mt-Hsp70–Tim44: the mt-Hsp70–Tim44 complex forms in the presence of ATP; ATP hydrolysis occurs while mt-Hsp70 is complexed with Tim44; Mge1p then promotes dissociation of the ADP-form of mt-Hsp70 from Tim44; and subsequently Mge1p promotes ADP release from mt-Hsp70 to allow re-binding of ATP. Biochemical reconstitution of the import cycle, nucleotide-dependent co-precipitation, Mge1p depletion assays in yeast The EMBO journal High 8918457
2004 Tim44 interacts with both the ATPase domain and the peptide-binding domain of mtHsp70 (Ssc1); binding of polypeptide substrate to mtHsp70 disrupts the Tim44–mtHsp70 interaction through concerted conformational changes involving both Hsp70 domains, providing a regulated release mechanism for efficient translocation. In vitro binding assays with domain mutants of mtHsp70, site-directed mutagenesis, in vivo functional complementation Nature structural & molecular biology High 15489862
1998 Mammalian Tim44 (mTim44) localizes to the mitochondrial inner membrane (including cristae), is imported in a membrane-potential-dependent manner, is proteolytically processed from ~50 kDa to ~44 kDa, and is peripherally associated with the membrane (extractable by Na2CO3 at pH 11.5). Transient expression with anti-FLAG immunofluorescence in COS7 cells, immunoelectron microscopy, mitochondrial import assay, protease protection, Na2CO3 extraction Proceedings of the National Academy of Sciences of the United States of America High 9419343
1998 Tim44 is not an essential structural component of the import channel but is specifically required for pulling folded domains across the inner membrane and promoting preprotein unfolding; its inactivation reduces import rate only ~30% for loosely folded substrates but severely impairs import of tightly folded domains without reducing the number of import sites. Conditional yeast tim44 mutant allele, in organello import assays with folded and unfolded substrates, electron microscopy of import sites The EMBO journal High 9687491
2001 Tim44 interacts with the beta-stranded core of the peptide-binding domain of mtHsp70; the alpha-helices A and B of the peptide-binding domain of mtHsp70 transmit the nucleotide state of the ATPase domain to the peptide-binding domain, and Tim44 interaction with this region coordinates preprotein binding and release of the mtHsp70–preprotein complex from the TIM23 translocase. Chimeric mtHsp70/DnaK proteins targeted to yeast mitochondria, co-precipitation, in organello import assays The Journal of biological chemistry High 11733493
2000 The ATPase domain of mtHsp70 is essential for and directly interacts with Tim44 in an ATP-sensitive manner; the peptide-binding domain and carboxy-terminal segment cannot bind Tim44 alone but enhance the ATPase domain–Tim44 interaction, clearly separating the mtHsp70–Tim44 interaction site from the substrate-binding site. Yeast two-hybrid system, co-precipitation of imported truncated mtHsp70 constructs in mitochondria Molecular and cellular biology High 10913171
1999 Recombinant Tim44 is an elongated monomer with a stably folded C-terminal domain; it binds strongly to liposomes containing phosphatidylcholine and cardiolipin via both electrostatic interactions and penetration of the polar head-group region, but only weakly to phosphatidylcholine-only liposomes. Limited proteolysis, analytical ultracentrifugation, liposome binding assays, phospholipid monolayer studies with recombinant Tim44 overexpressed in E. coli Proceedings of the National Academy of Sciences of the United States of America High 10430866
2002 A single cysteine residue, Cys-369, located in the C-terminal domain of yeast Tim44 is exposed to the mitochondrial intermembrane space, establishing the topology of Tim44 in the inner membrane. Biotin maleimide (membrane-impermeable MPB) labeling of intact mitochondria followed by immunoprecipitation of modified Tim44 Biochemical and biophysical research communications Medium 12054602
2002 The peptide-binding domain of Ssc1 (mtHsp70) sustains Tim44 binding, while the peptide-binding domains of the paralogous Ssc3 and Ssq1 exert a negative effect on ATPase domain–Tim44 interaction; a mutation in the Ssc1 peptide-binding domain similarly negatively affects ATPase domain–Tim44 interaction, demonstrating that the peptide-binding domain regulates Tim44 interaction through interdomain communication. Chimeric Hsp70 protein construction, co-precipitation assays, yeast in vivo complementation The EMBO journal Medium 12032075
1999 An 18-residue J-related segment of Tim44 is essential for productive interaction with mtHsp70; deletion of this segment (Tim44Δ18) assembles correctly at the inner membrane import site but weakens mtHsp70 binding in an ATP-regulated manner, reducing unfolding of tightly folded preproteins and overall import efficiency; the segment is essential for cell viability. Deletion mutagenesis in Saccharomyces cerevisiae, co-expression with wild-type Tim44, in organello import assays, co-precipitation The Journal of cell biology High 10352014
2008 Tim44 plays a differential role in recruiting PAM modules to the TIM23 translocase: in tim44-804 yeast mutant mitochondria the J-complex (Pam18/Pam16) association with TIM23 is impaired, whereas Pam17 binding is unexpectedly increased; Pam17 interacts directly with the channel protein Tim23, revealing a Tim44-independent interaction site. Conditional yeast tim44 mutant allele (tim44-804), co-immunoprecipitation, co-purification of TIM23 complexes Molecular biology of the cell High 18400944
2008 The N-terminal 167-amino-acid segment of mature Tim44 is sufficient for interaction with mtHsp70 and for destabilization of the Tim44–mtHsp70 complex by substrate peptide binding; a 30-amino-acid region within this segment affects both mtHsp70 release upon peptide binding and Tim44 interaction with the TIM23 translocon. N-terminal truncation and alanine-scanning mutagenesis, in vitro binding assays, yeast in vivo complementation Molecular and cellular biology High 18426906
2007 Crystal structure of human Tim44 C-terminal domain at 1.9 Å resolution reveals an NTF2-like fold; pentaethylene glycol (mimicking lipid) binds at two sites—a large hydrophobic cavity and a loop between α1 and α2 helices near Pro308 (site of familial oncocytic thyroid carcinoma mutation P308Q); lipid binding induces conformational changes around the α1–α2 loop including slippage of the α1 helix. X-ray crystallography at 1.9 Å resolution Acta crystallographica. Section D, Biological crystallography High 18084070
2009 The N-terminal α-helix (helix A1) of the Tim44 C-terminal domain is required for association with cardiolipin-containing phospholipid vesicles; truncation removing helix A1 abolishes cardiolipin binding, and molecular dynamics simulations indicate lipid hydrophobic tails interact with Tim44 via its hydrophobic cavity while helices A1 and A2 serve as the membrane attachment site. N-terminal truncation mutants of yeast Tim44, liposome binding assays, molecular dynamics simulations Biochemistry Medium 19863062
2009 Pam17 acts at an early stage and Tim44 at a later step of protein translocation into the mitochondrial matrix; genetic synthetic interactions between PAM17 and TIM44 indicate functional cooperation in the PAM import motor. Genetic epistasis (synthetic lethality/interaction analysis), in organello import assays The international journal of biochemistry & cell biology Medium 19577659
2011 The N-terminal helices A1 and A2 of Tim44-CTD are crucial for inner mitochondrial membrane tethering; these amphipathic helices can expose their hydrophobic face during membrane binding or conceal it in the soluble form, functioning as a membrane sensor for Tim44 anchoring of the PAM complex to TIM23. X-ray crystallography of Tim44-CTD, biochemical membrane binding assays Protein and peptide letters Medium 21342097
2017 Both domains of Tim44 interact with the major matrix-exposed loop of Tim23 (with CTD also binding Tim17); the NTD of Tim44 is intrinsically disordered and binds incoming presequence near a region important for Hsp70 and Tim23 interaction; the CTD primarily anchors Tim44 to the translocon while the NTD acts as a dynamic arm interacting with multiple components to drive translocation. Site-specific in vivo crosslinking in S. cerevisiae, genetic approaches, in vitro NTD binding assays eLife High 28440746
2017 The small molecule MB-10 (MitoBloCK-10) inhibits TIM23-dependent preprotein import by binding to a specific pocket in the C-terminal domain of Tim44; this C-terminal region is required for binding to the translocating precursor and binding to mtHsp70 under low-ATP conditions. Genetic screen (Ura3 mistargeting assay), site-directed mutagenesis, molecular docking, molecular dynamics simulations, biochemical import assays The Journal of biological chemistry Medium 28167535
2000 Tim44 is required for efficient recruitment of mtHsp70 to translocating preproteins; after Tim44 inactivation, mtHsp70 binding to the frataxin homolog Yfh1p and to DHFR during translocation is nearly completely blocked, impairing proper folding of newly imported proteins and causing increased aggregation. Conditional tim44 mutant yeast, co-immunoprecipitation of mtHsp70 with translocating substrates, in organello folding assays European journal of biochemistry Medium 10824101
2005 Mammalian Tim44 facilitates mitochondrial import of antioxidative enzymes superoxide dismutase and glutathione peroxidase; Tim44 overexpression in human aortic smooth muscle cells normalizes high-glucose-induced ROS production, increases ATP production, and restores inner membrane potential. siRNA knockdown and pcDNA3.1/TIM44 overexpression in human aortic smooth muscle cells, ROS measurement, ATP assay, mitochondrial membrane potential measurement Diabetes Medium 16186389
2016 TIMM44 knockdown via siRNA reduces SOD2 (superoxide dismutase 2) levels, leading to elevated ROS that activates autophagy and apoptosis through the ROS–Akt–mTOR pathway in colorectal cancer cells; the TIM44–SOD2–ROS–mTOR pathway mediates the anticancer effects of the mitochondria-targeting compound IR-58. siRNA interference, RNA sequencing, mass spectrometry, small-molecule treatment (IR-58) in colorectal cancer cells and xenografts Gut Medium 27849558
2020 HuR binds to the 3′UTR of TIMM44 mRNA and stabilizes it; luciferase reporter assay with the TIMM44 3′UTR confirmed direct HuR–TIMM44 mRNA interaction, and HuR-dependent promotion of ovarian cancer cell proliferation is mediated through TIMM44 mRNA stabilization. Luciferase reporter assay with TIMM44 3′UTR, HuR overexpression/knockdown, TIMM44 siRNA in ovarian cancer cell lines Cell biochemistry and biophysics Medium 32901414

Source papers

Stage 0 corpus · 30 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 The Tim core complex defines the number of mitochondrial translocation contact sites and can hold arrested preproteins in the absence of matrix Hsp70-Tim44. The EMBO journal 250 9312000
1996 Differential requirement for the mitochondrial Hsp70-Tim44 complex in unfolding and translocation of preproteins. The EMBO journal 97 8654364
1996 The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import. The EMBO journal 96 8918457
2004 Regulated interactions of mtHsp70 with Tim44 at the translocon in the mitochondrial inner membrane. Nature structural & molecular biology 88 15489862
1998 Characterization of mammalian translocase of inner mitochondrial membrane (Tim44) isolated from diabetic newborn mouse kidney. Proceedings of the National Academy of Sciences of the United States of America 60 9419343
1998 Separation of structural and dynamic functions of the mitochondrial translocase: Tim44 is crucial for the inner membrane import sites in translocation of tightly folded domains, but not of loosely folded preproteins. The EMBO journal 54 9687491
2008 Mitochondrial protein import motor: differential role of Tim44 in the recruitment of Pam17 and J-complex to the presequence translocase. Molecular biology of the cell 53 18400944
2016 Identification of a fluorescent small-molecule enhancer for therapeutic autophagy in colorectal cancer by targeting mitochondrial protein translocase TIM44. Gut 52 27849558
2006 Novel germline variants identified in the inner mitochondrial membrane transporter TIMM44 and their role in predisposition to oncocytic thyroid carcinomas. British journal of cancer 49 17088905
2001 Mitochondrial protein import: molecular basis of the ATP-dependent interaction of MtHsp70 with Tim44. The Journal of biological chemistry 49 11733493
2000 Mitochondrial protein import motor: the ATPase domain of matrix Hsp70 is crucial for binding to Tim44, while the peptide binding domain and the carboxy-terminal segment play a stimulatory role. Molecular and cellular biology 49 10913171
1999 Domain structure and lipid interaction of recombinant yeast Tim44. Proceedings of the National Academy of Sciences of the United States of America 46 10430866
2017 Dual interaction of scaffold protein Tim44 of mitochondrial import motor with channel-forming translocase subunit Tim23. eLife 40 28440746
1999 The J-related segment of tim44 is essential for cell viability: a mutant Tim44 remains in the mitochondrial import site, but inefficiently recruits mtHsp70 and impairs protein translocation. The Journal of cell biology 38 10352014
2008 Residues of Tim44 involved in both association with the translocon of the inner mitochondrial membrane and regulation of mitochondrial Hsp70 tethering. Molecular and cellular biology 37 18426906
2005 Gene delivery of Tim44 reduces mitochondrial superoxide production and ameliorates neointimal proliferation of injured carotid artery in diabetic rats. Diabetes 37 16186389
2002 The Hsp70 peptide-binding domain determines the interaction of the ATPase domain with Tim44 in mitochondria. The EMBO journal 33 12032075
2022 TIMM44 is a potential therapeutic target of human glioma. Theranostics 28 36438483
2009 Interaction of the Tim44 C-terminal domain with negatively charged phospholipids. Biochemistry 28 19863062
2009 Pam17 and Tim44 act sequentially in protein import into the mitochondrial matrix. The international journal of biochemistry & cell biology 22 19577659
2020 HuR Promotes Ovarian Cancer Cell Proliferation by Regulating TIMM44 mRNA Stability. Cell biochemistry and biophysics 18 32901414
2007 Structure of the human Tim44 C-terminal domain in complex with pentaethylene glycol: ligand-bound form. Acta crystallographica. Section D, Biological crystallography 17 18084070
2023 The mitochondrial protein TIMM44 is required for angiogenesis in vitro and in vivo. Cell death & disease 14 37147302
2017 Adaptation of a Genetic Screen Reveals an Inhibitor for Mitochondrial Protein Import Component Tim44. The Journal of biological chemistry 14 28167535
2000 Biogenesis of the yeast frataxin homolog Yfh1p. Tim44-dependent transfer to mtHsp70 facilitates folding of newly imported proteins in mitochondria. European journal of biochemistry 13 10824101
2024 A first-in-class TIMM44 blocker inhibits bladder cancer cell growth. Cell death & disease 10 38467612
1997 Coupling chemical energy by the hsp70/tim44 complex to drive protein translocation into mitochondria. Journal of bioenergetics and biomembranes 7 9067799
2011 Membrane binding mechanism of yeast mitochondrial peripheral membrane protein TIM44. Protein and peptide letters 5 21342097
2002 Probing the membrane topology of a subunit of the mitochondrial protein translocase, Tim44, with biotin maleimide. Biochemical and biophysical research communications 2 12054602
2026 Mechanistic study of TIMM44 mediating gastric carcinogenesis via the Gαi1-PI3K-AKT-mTOR signaling pathway. Scientific reports 0 42086642

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