{"artifact":{"id":"paper-fig-paper-41899560-1","artifact_type":"paper_figure","entity_ids":"[]","title":"Figure 1 — TFE3-Rearranged and TFEB-Altered Renal Cell Carcinomas: Molecular Landscape and ","quality_score":0.5,"created_by":"paper_figures_tool","provenance_chain":"[{\"step\": \"paper_figures_backfill\", \"pmid\": \"paper-41899560\", \"timestamp\": \"2026-04-22T01:29:42.335045\"}]","content_hash":null,"metadata":{"pmid":"paper-41899560","caption":"Integrated mechanistic model of MiT-RCC driven by  TFE3  and  TFEB  alterations. In  TFE3 -rearranged RCC, most fusions join a 5′ partner gene to the 3′ portion of  TFE3 , preserving the C-terminal DNA-binding and dimerization domains and promoting constitutive nuclear activity;  TFEB -rearranged tumors are driven by analogous transcriptional deregulation, whereas  TFEB -amplified RCC is biologically distinct. These events activate a core MiT/TFE transcriptional program that rewires tumor cell metabolism and stress-adaptation pathways. In fusion-driven translocation RCC (tRCC),  TFE3 / TFEB  fusions induce upregulation of  PPARGC1A  (PGC-1α), promoting mitochondrial biogenesis and increased dependency on oxidative phosphorylation (OXPHOS), which creates context-specific metabolic vulnerabilities. In parallel, sustained activation of the mTOR-lysosome axis enhances lysosomal biogenesis and autophagy, supporting tumor survival under metabolic stress and reflecting partial uncoupling of M","image_url":"https://www.ebi.ac.uk/europepmc/articles/PMC13025244/bin/cancers-18-00958-g001.jpg","paper_title":"TFE3-Rearranged and TFEB-Altered Renal Cell Carcinomas: Molecular Landscape and Therapeutic Advances.","figure_label":"Figure 1","figure_number":1,"_schema_version":1,"source_strategy":"pmc_api"},"created_at":"2026-04-21T18:29:40.747630-07:00","updated_at":"2026-04-21T18:29:40.747630-07:00","version_number":4,"parent_version_id":null,"version_tag":null,"changelog":null,"is_latest":1,"lifecycle_state":"active","superseded_by":null,"deprecated_at":null,"deprecated_reason":null,"dependencies":null,"market_price":0.5,"origin_type":"external","origin_url":null,"lifecycle_changed_at":"2026-04-21T18:29:40.747630-07:00","citation_count":0,"embed_count":0,"derivation_count":0,"support_count":0,"contradiction_count":0,"total_usage":0.0,"usage_score":0.5,"usage_computed_at":null,"quality_status":null,"contributors":[],"answers_question_ids":null,"deprecated_reason_detail":null,"deprecated_reason_code":null,"commit_sha":null,"commit_submodule":null,"last_mutated_at":"2026-05-16T14:51:34.657673-07:00","disputed_at":null,"gap_id":null,"mission_id":null,"intrinsic_priority":null,"effective_priority":null,"artifact_id":"2f00243f-3657-42c8-b96f-7056abddeaf4","artifact_dir":null,"primary_filename":null,"accessory_filenames":null,"folder_layout_version":1,"migrated_to_folder_at":null,"hypothesis_id":null,"authorship":{"kind":"human","contributors":[{"role":"author","actor_ref":"paper_figures_tool"}]},"epistemic_tier":"T3_provisional","created_by_agent_id":null},"outgoing_links":[],"incoming_links":[],"current_artifact_id":"paper-fig-paper-41899560-1","is_canonical":true,"supersede_chain":["paper-fig-paper-41899560-1"]}