{"gene":"PF3D7_0808450","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2016,"finding":"MPODD (PF3D7_0808450 homologue) is a small mitochondrial protein essential for ookinete development and mosquito transmission in Plasmodium berghei; knockout parasites displayed malformed ookinetes unable to transmit, with reduced mitochondrial mass but no disruption of organelle integrity, indicating a role in mitochondrial import or metabolism rather than biogenesis or morphology maintenance.","method":"Gene knockout in P. berghei with phenotypic analysis (mitochondrial mass measurement, ookinete morphology), genetic complementation with P. falciparum homologue (PF3D7_0808450) rescuing the mpodd− phenotype","journal":"Open biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype and cross-species complementation rescue, single lab, two orthogonal methods","pmids":["27053680"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"The P. falciparum homologue of MPODD (PF3D7_0808450) is functionally conserved with its P. berghei counterpart, as demonstrated by genetic complementation: expression of PF3D7_0808450 rescues the mpodd− ookinete developmental defect phenotype in P. berghei.","method":"Genetic complementation (expression of PF3D7_0808450 in P. berghei mpodd− parasites with phenotypic rescue readout)","journal":"Open biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct rescue experiment with defined phenotypic readout, single lab, single method","pmids":["27053680"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"finding":"A complexome-based proteomic analysis of P. falciparum mitochondrial protein complexes demonstrated co-migration of the PF3D7_0808450 (MPODD) homologue with PfSdhA and PfSdhB, placing MPODD as a candidate membrane-anchoring component of the succinate dehydrogenase (SDH) complex in P. falciparum.","method":"Complexome-based proteomic analysis (co-migration of MPODD homologue with SDH catalytic subunits PfSdhA and PfSdhB on native gels/fractionation)","journal":"Open biology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — co-migration data cited as supporting evidence from a referenced complexome study; no direct functional validation in P. falciparum reported in this abstract","pmids":["38835243"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"MPODD (PF3D7_0808450) is a myzozoan-specific small mitochondrial protein that functions as a membrane-anchoring component of the succinate dehydrogenase (SDH) complex; in Plasmodium berghei it is essential for ookinete development and mosquito transmission, reducing mitochondrial mass when knocked out, and the P. falciparum homologue (PF3D7_0808450) is functionally conserved as shown by cross-species genetic complementation rescue of the ookinete defect."},"narrative":{"mechanistic_narrative":"MPODD (PF3D7_0808450) is a small myzozoan mitochondrial protein required for parasite development and mosquito transmission [PMID:27053680]. In Plasmodium berghei, knockout of the MPODD orthologue produces malformed ookinetes that cannot transmit and reduces mitochondrial mass without disrupting organelle integrity, a phenotype consistent with a role in mitochondrial import or metabolism rather than in organelle biogenesis or morphology maintenance [PMID:27053680]. The P. falciparum gene PF3D7_0808450 is functionally conserved with its P. berghei counterpart: its expression rescues the ookinete developmental defect of P. berghei mpodd− parasites [PMID:27053680]. Beyond this genetic characterization, the molecular activity of MPODD is defined only by a P. falciparum complexome analysis in which the MPODD homologue co-migrates with the succinate dehydrogenase catalytic subunits PfSdhA and PfSdhB, positioning it as a candidate membrane-anchoring component of the SDH complex [PMID:38835243]. No direct biochemical or functional validation of MPODD within the SDH complex in P. falciparum has been reported in the available corpus.","teleology":[{"year":2016,"claim":"Establishing that a small mitochondrial protein is required for parasite transmission, the study defined MPODD as essential for ookinete development while distinguishing a metabolic/import role from organelle biogenesis.","evidence":"Gene knockout in P. berghei with ookinete morphology and mitochondrial mass measurement","pmids":["27053680"],"confidence":"Medium","gaps":["The specific molecular activity underlying the mitochondrial mass reduction was not identified","Whether the defect reflects impaired import versus impaired metabolism was not resolved","No characterization of MPODD in asexual blood stages"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2016,"claim":"To test functional conservation of the P. falciparum gene, cross-species complementation showed PF3D7_0808450 can substitute for the P. berghei orthologue, validating PF3D7_0808450 as a functional MPODD.","evidence":"Genetic complementation of P. berghei mpodd− with PF3D7_0808450 and phenotypic rescue readout","pmids":["27053680"],"confidence":"Medium","gaps":["Rescue demonstrates functional equivalence but does not define the biochemical function","No direct phenotype from disruption of PF3D7_0808450 in P. falciparum itself"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2024,"claim":"To place MPODD in a molecular pathway, a complexome analysis found the P. falciparum MPODD homologue co-migrating with SDH catalytic subunits, proposing it as a membrane-anchoring component of the succinate dehydrogenase complex.","evidence":"Complexome-based proteomic co-migration with PfSdhA and PfSdhB","pmids":["38835243"],"confidence":"Low","gaps":["Co-migration alone does not establish stable physical association or a structural role","No direct functional validation of MPODD within the SDH complex was reported","Whether SDH association explains the transmission phenotype is untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The biochemical mechanism by which MPODD supports mitochondrial function and its precise role within the SDH complex remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No reconstitution or interaction validation of MPODD with SDH subunits","No structural model or membrane-topology data for MPODD","Mechanistic link between SDH association and the ookinete/transmission defect unresolved"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Candidate component of the succinate dehydrogenase (SDH) complex (co-migration with PfSdhA/PfSdhB) [#2]"],"partners":["PFSDHA (CO-MIGRATION) [#2]","PFSDHB (CO-MIGRATION) [#2]"],"other_free_text":["Essential for ookinete development and mosquito transmission in P. berghei; knockout reduces mitochondrial mass without disrupting organelle integrity [#0]","P. falciparum PF3D7_0808450 is functionally conserved and rescues the P. berghei mpodd− phenotype by complementation [#0, #1]","Described as a myzozoan-specific small mitochondrial protein [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"27053680","id":"PMC_27053680","title":"A small mitochondrial protein present in myzozoans is essential for malaria transmission.","date":"2016","source":"Open biology","url":"https://pubmed.ncbi.nlm.nih.gov/27053680","citation_count":17,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MPODD"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38835243","id":"","title":"A myzozoan-specific protein is an essential membrane-anchoring component of the succinate dehydrogenase complex in Toxoplasma parasites.","date":"2024","source":"Open biology","url":"https://pubmed.ncbi.nlm.nih.gov/38835243","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["MPODD"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4407,"output_tokens":1025,"usd":0.014298,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5768,"output_tokens":1926,"usd":0.038495,"stage2_stop_reason":"end_turn"},"total_usd":0.052793,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"MPODD (PF3D7_0808450 homologue) is a small mitochondrial protein essential for ookinete development and mosquito transmission in Plasmodium berghei; knockout parasites displayed malformed ookinetes unable to transmit, with reduced mitochondrial mass but no disruption of organelle integrity, indicating a role in mitochondrial import or metabolism rather than biogenesis or morphology maintenance.\",\n      \"method\": \"Gene knockout in P. berghei with phenotypic analysis (mitochondrial mass measurement, ookinete morphology), genetic complementation with P. falciparum homologue (PF3D7_0808450) rescuing the mpodd− phenotype\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype and cross-species complementation rescue, single lab, two orthogonal methods\",\n      \"pmids\": [\"27053680\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"The P. falciparum homologue of MPODD (PF3D7_0808450) is functionally conserved with its P. berghei counterpart, as demonstrated by genetic complementation: expression of PF3D7_0808450 rescues the mpodd− ookinete developmental defect phenotype in P. berghei.\",\n      \"method\": \"Genetic complementation (expression of PF3D7_0808450 in P. berghei mpodd− parasites with phenotypic rescue readout)\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct rescue experiment with defined phenotypic readout, single lab, single method\",\n      \"pmids\": [\"27053680\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"A complexome-based proteomic analysis of P. falciparum mitochondrial protein complexes demonstrated co-migration of the PF3D7_0808450 (MPODD) homologue with PfSdhA and PfSdhB, placing MPODD as a candidate membrane-anchoring component of the succinate dehydrogenase (SDH) complex in P. falciparum.\",\n      \"method\": \"Complexome-based proteomic analysis (co-migration of MPODD homologue with SDH catalytic subunits PfSdhA and PfSdhB on native gels/fractionation)\",\n      \"journal\": \"Open biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — co-migration data cited as supporting evidence from a referenced complexome study; no direct functional validation in P. falciparum reported in this abstract\",\n      \"pmids\": [\"38835243\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"MPODD (PF3D7_0808450) is a myzozoan-specific small mitochondrial protein that functions as a membrane-anchoring component of the succinate dehydrogenase (SDH) complex; in Plasmodium berghei it is essential for ookinete development and mosquito transmission, reducing mitochondrial mass when knocked out, and the P. falciparum homologue (PF3D7_0808450) is functionally conserved as shown by cross-species genetic complementation rescue of the ookinete defect.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"MPODD (PF3D7_0808450) is a small myzozoan mitochondrial protein required for parasite development and mosquito transmission [#0]. In Plasmodium berghei, knockout of the MPODD orthologue produces malformed ookinetes that cannot transmit and reduces mitochondrial mass without disrupting organelle integrity, a phenotype consistent with a role in mitochondrial import or metabolism rather than in organelle biogenesis or morphology maintenance [#0]. The P. falciparum gene PF3D7_0808450 is functionally conserved with its P. berghei counterpart: its expression rescues the ookinete developmental defect of P. berghei mpodd\\u2212 parasites [#0, #1]. Beyond this genetic characterization, the molecular activity of MPODD is defined only by a P. falciparum complexome analysis in which the MPODD homologue co-migrates with the succinate dehydrogenase catalytic subunits PfSdhA and PfSdhB, positioning it as a candidate membrane-anchoring component of the SDH complex [#2]. No direct biochemical or functional validation of MPODD within the SDH complex in P. falciparum has been reported in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Establishing that a small mitochondrial protein is required for parasite transmission, the study defined MPODD as essential for ookinete development while distinguishing a metabolic/import role from organelle biogenesis.\",\n      \"evidence\": \"Gene knockout in P. berghei with ookinete morphology and mitochondrial mass measurement\",\n      \"pmids\": [\"27053680\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"The specific molecular activity underlying the mitochondrial mass reduction was not identified\",\n        \"Whether the defect reflects impaired import versus impaired metabolism was not resolved\",\n        \"No characterization of MPODD in asexual blood stages\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"To test functional conservation of the P. falciparum gene, cross-species complementation showed PF3D7_0808450 can substitute for the P. berghei orthologue, validating PF3D7_0808450 as a functional MPODD.\",\n      \"evidence\": \"Genetic complementation of P. berghei mpodd\\u2212 with PF3D7_0808450 and phenotypic rescue readout\",\n      \"pmids\": [\"27053680\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Rescue demonstrates functional equivalence but does not define the biochemical function\",\n        \"No direct phenotype from disruption of PF3D7_0808450 in P. falciparum itself\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"To place MPODD in a molecular pathway, a complexome analysis found the P. falciparum MPODD homologue co-migrating with SDH catalytic subunits, proposing it as a membrane-anchoring component of the succinate dehydrogenase complex.\",\n      \"evidence\": \"Complexome-based proteomic co-migration with PfSdhA and PfSdhB\",\n      \"pmids\": [\"38835243\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Co-migration alone does not establish stable physical association or a structural role\",\n        \"No direct functional validation of MPODD within the SDH complex was reported\",\n        \"Whether SDH association explains the transmission phenotype is untested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical mechanism by which MPODD supports mitochondrial function and its precise role within the SDH complex remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No reconstitution or interaction validation of MPODD with SDH subunits\",\n        \"No structural model or membrane-topology data for MPODD\",\n        \"Mechanistic link between SDH association and the ookinete/transmission defect unresolved\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"Candidate component of the succinate dehydrogenase (SDH) complex (co-migration with PfSdhA/PfSdhB) [#2]\"],\n    \"partners\": [\"PfSdhA (co-migration) [#2]\", \"PfSdhB (co-migration) [#2]\"],\n    \"other_free_text\": [\n      \"Essential for ookinete development and mosquito transmission in P. berghei; knockout reduces mitochondrial mass without disrupting organelle integrity [#0]\",\n      \"P. falciparum PF3D7_0808450 is functionally conserved and rescues the P. berghei mpodd\\u2212 phenotype by complementation [#0, #1]\",\n      \"Described as a myzozoan-specific small mitochondrial protein [#0]\"\n    ]\n  }\n}\n```","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0808450","name":null,"product":"protein MPODD, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1222200","name":null,"product":"protein MPODD","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0110250","name":null,"product":"protein MPODD, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"MPODD","evaluation":null}