{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:15:12Z","timestamp":1788434112870,"version":"build-2803163510"},"reference-count":111,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sistema Nacional de Investigaci\u00f3n de Panam\u00e1"},{"DOI":"10.13039\/501100007061","name":"National Secretariat of Science, Technology and Innovation","doi-asserted-by":"publisher","award":["DDCCT No. 083-2025"],"award-info":[{"award-number":["DDCCT No. 083-2025"]}],"id":[{"id":"10.13039\/501100007061","id-type":"DOI","asserted-by":"publisher"}]},{"award":["DDCCT No. 083-2025"],"award-info":[{"award-number":["DDCCT No. 083-2025"]}],"id":[{"id":"https:\/\/ror.org\/03gat5t60","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Programmed cell death pathways in Plasmodium falciparum remain conceptually fragmented. Over decades, researchers have applied metazoan apoptotic, autophagic, and necrotic markers to this deep-branching protozoan, frequently clashing with the reality that the parasite lacks the canonical genetic machinery (such as true caspases or death receptors) found in multicellular eukaryotes. In this work, we shift the focus from the parasite\u2019s disputed intrinsic death machinery to the host\u2013parasite interaction arena: the active manipulation of the host erythrocyte\u2019s autonomous suicide program, eryptosis. The intraerythrocytic development of P. falciparum generates profound oxidative stress through hemoglobin digestion and free heme release, driving lipid peroxidation and the accumulation of reactive aldehydes such as 4-hydroxynonenal (4-HNE)\u2014potent signaling molecules that can trigger eryptotic pathways. We integrate existing literature on membrane remodeling, protein export, and lipid raft dynamics to propose a novel Host Protein Sequestration Hypothesis. We suggest that P. falciparum evades splenic clearance by actively dismantling the host cell\u2019s surface death signaling platforms\u2014Clusters of Apoptotic Signaling Molecule-Enriched Rafts (CASMERs)\u2014and pulling these host components inward. We suggest that human FAS (CD95) is internalized by the parasite and physically interacts with Plasmodium lipid-raft scaffolding proteins, preventing it from engaging FasL (CD178) that is either expressed on adjacent erythrocytes or presented within the local splenic microenvironment\u2014an interaction that would otherwise precipitate eryptotic signaling. This perspective offers a fundamentally fresh conceptual framework for understanding malaria survival strategies and highlights a vulnerable, non-canonical therapeutic target.<\/jats:p>","DOI":"10.3390\/cells15171603","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:10:33Z","timestamp":1788430233000},"page":"1603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulation of Host Cell Death Signaling Platforms by Plasmodium falciparum: Implications for Eryptosis Regulation and Parasite Survival"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8495-1580","authenticated-orcid":false,"given":"Lina","family":"Sol\u00eds-Castillero","sequence":"first","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Molecular de Enfermedades (CBCMe), Instituto de Investigaciones Cient\u00edficas y Servicios de Alta Tecnolog\u00eda (INDICASAT AIP), City of Knowledge, Panama City ACC92-D5Q28, Panama"},{"name":"Laboratorio Cl\u00ednico Genetix, Panama City AGC92-MG52D, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5475-5407","authenticated-orcid":false,"given":"Ricardo","family":"Correa","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Molecular de Enfermedades (CBCMe), Instituto de Investigaciones Cient\u00edficas y Servicios de Alta Tecnolog\u00eda (INDICASAT AIP), City of Knowledge, Panama City ACC92-D5Q28, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2766-7361","authenticated-orcid":false,"given":"Maria Fernanda","family":"Alves-Rosa","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Molecular de Enfermedades (CBCMe), Instituto de Investigaciones Cient\u00edficas y Servicios de Alta Tecnolog\u00eda (INDICASAT AIP), City of Knowledge, Panama City ACC92-D5Q28, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3002-9467","authenticated-orcid":false,"given":"Carmenza","family":"Spadafora","sequence":"additional","affiliation":[{"name":"Centro de Biolog\u00eda Celular y Molecular de Enfermedades (CBCMe), Instituto de Investigaciones Cient\u00edficas y Servicios de Alta Tecnolog\u00eda (INDICASAT AIP), City of Knowledge, Panama City ACC92-D5Q28, Panama"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00294-008-0214-x","article-title":"Drug resistance and genetic mapping in Plasmodium falciparum","volume":"54","author":"Hayton","year":"2008","journal-title":"Curr. 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