Direct decisions preserve the complete source annotation and the corresponding review. Binding records retain exact partner identities and methods. MitoCoP target records distinguish mitochondrial detection from submitochondrial topology.
The primary 2023 study, PMID36896912 establishes outer-membrane localization, SKP1/CUL1 association, receptor ubiquitination/turnover and mitophagy restraint. Read the submitochondrial-localization Methods and Results on protease accessibility, alkaline extraction, N-terminal targeting constructs and receptor rescue. PMID37161784 independently uses mitochondrial swelling and TOM20 versus TIM50 microscopy, F-box perturbation, receptor half-life and cellular ubiquitination. Its available antibodies did not reliably detect endogenous FBXL4; tagging/expression conditions remain relevant. PMID37102372 distinguishes receptor association from SCF association and establishes NIX-dominant rescue in RPE1 cells, without making that dominance universal. BioID is proximity, co-IP is complex association, and neither automatically establishes purified binary binding.
PMID32525278 measures increased lysosome-dependent mitochondrial removal in deficient human cells and mouse material. Its turnover/inhibitor/mito-QC results support restraint of mitophagy; FBXL4 does not thereby become the machinery that digests mitochondria. The earlier source-specific LC3 interpretation is retained separately from later BNIP3/NIX mechanisms. PMID23993193 provides human disease-gene and fibroblast rescue/mitochondrial-colocalization evidence, without demonstrating FBXL4 DNA-replication chemistry or an exact membrane topology.
PMID38992176 distinguishes substrate recruitment from SCF assembly: FBXL4 still associates with SKP1/CUL1 after PPTC7 loss. Its Results on interface mutants, turnover and mitophagy support cooperation, but the Discussion explicitly distinguishes a modeled ternary arrangement from experimental proof of simultaneous ternary occupancy. ITC tests PPTC7 with receptor peptides, not purified FBXL4 with those peptides. The catalytically impaired D290N rescue has a residual-activity caveat.
PMID40025034 supplies independent human-cell co-IP, turnover/rescue and denaturing cellular ubiquitination assays. Although called in vivo by the paper, the ubiquitination experiment is an in-cell assay, not purified reconstitution. The paper's new protease/fractionation experiments assay PPTC7 and BNIP3/BNIP3L, taking FBXL4 outer-membrane location as a cited premise. They are not an additional independent FBXL4 topology measurement. Neither study assigns independent E3 catalysis to PPTC7.
The two studies report different PPTC7 D78A outcomes and different effects of excess component expression. The U2OS/293T and DFP conditions in PMID38992176 differ from the later HeLa setting. Preserve the discrepancy: neither a universal monotonic dose-response relationship nor an established stoichiometric explanation follows. Proposed evolutionary origin and complex stoichiometry remain hypotheses.
The original PMID23993194 was read beyond its abstract, including Figure 4, the localization Results and protease/fractionation Methods. Tagged human FBXL4 was protected from trypsin in intact mitochondrial preparations but accessible after digitonin; separate mouse-liver fractionation supported a soluble pool. These positive experiments conflict with later outer-membrane results. Expression, preparations and protease conditions differ, and the 2013 Results and Methods print different trypsin-concentration units. Exact intermembrane-space localization remains unresolved; the old experiment is not dismissed as never performed. Engineered targeting constructs are not natural splice or cleavage products.
The MitoCoP paper, PMID34800366, includes Q9UKA2/FBXL4 in original Tables S1B, S2B/E/G and S3A/C. The exact row joins are supplied in the linked target-record table. The spatial multi-cell-line row is positive in HEK, HeLa and Huh7; its U2OS mitochondrial-cluster cell is blank. The carbonate/sonication row is assigned the ambiguous membrane-association cluster. This source positively supports mitochondrion and is not narrowed to outer membrane. Read the Methods for subtractive proteomics, clustering, TOMM40 importomics and carbonate/sonication, together with those target rows.
The genuine PMID32814053 original and supplements contain the exact FBXL4 pairs. Table S2 (mmc3.xlsx), sheet NN1.0 rows 3485–3486 and NN1.0ext rows 7569–7570, lists DNM2 and TPP1 with FBXL4. IntAct study IM-28217 retains Q9UKA2–O14773 and Q9UKA2–P50570-2 in array, pooling and validated two-hybrid records. Original Results pp. 2–4 and Methods p. e8 describe yeast reporter controls and pairwise retesting. The gene-level supplementary table and exact isoform-resolved IntAct records are distinct levels of identification.
Official GO:0002020 protease binding and GO:0051020 GTPase binding describe binding to the relevant enzyme class; they do not assert regulation or catalysis by the binding protein. Official UniProt identities establish TPP1 as a peptidase and DNM2 as dynamin-2/GTPase. These terms therefore refine the two generic-binding records without adding binding cores. The small-GTPase-binding child is inappropriate for dynamin. Top-target Table S1 gives TPP1 clone CCSB_992 and DNM2 clone IOH28879, but no insert coordinates; IntAct feature fields are also empty. No mapped mature TPP1 chain, full-length tested construct, physiological colocalization, SCF-substrate relationship or membrane-remodeling mechanism is inferred. These exact pairs were not recovered among the separate DULIP-validation workbook target hits; no mammalian validation is claimed for them.
The PMID10531035 original author PDF, Figure 1 and supplemental Methods/captions identify Fbl4 by database search. Representative Fbx4 assays must not be silently transferred to Fbl4/FBXL4. Later target experiments support SCF association and its proteasomal substrate-turnover role; the general ubiquitin-ligase-complex and ubiquitin-dependent-catabolism terms add no separate mechanism to their retained specific descendants.
PMID21757720, Results and JMJD2A/KDM4A turnover/co-IP Methods, supports a contextual FBXL4-associated turnover role in HeLa/HEK293T cells. Immobilized substrate incubated with lysate is not a purified binary assay, and a nuclear substrate does not independently image nuclear FBXL4. PMID33234069 is a family review; PMID36135912 is a mitochondrial-dynamics review. Neither supplies a new target structure or direct fusion chemistry assay.
The inherited provider report remains an unmodified research aid. Each manual PMID assessment distinguishes the primary text actually read, original assay scope and unavailable supplementary/pixel detail. Four independent database-lane primary read scopes (PMIDs36896912, 37161784, 23993194 and 21757720) are already included once in the corresponding complete reference assessments; integration should not append them a second time.