biostudies-literatureKhalfi PLigue Contre le CancerMinistère de la RechercheInstitut PasteurCentre National de la Recherche Scientifiquee1011170https://www.ebi.ac.uk/biostudies/studies/S-EPMC9983871biostudies-literatureUnknown19(2)Viruses have evolved countless mechanisms to subvert and impair the host innate immune response. Measles virus (MeV), an enveloped, non-segmented, negative-strand RNA virus, alters the interferon response through different mechanisms, yet no viral protein has been described as directly targeting mitochondria. Among the crucial mitochondrial enzymes, 5'-aminolevulinate synthase (ALAS) is an enzyme that catalyzes the first step in heme biosynthesis, generating 5'-aminolevulinate from glycine and succinyl-CoA. In this work, we demonstrate that MeV impairs the mitochondrial network through the V protein, which antagonizes the mitochondrial enzyme ALAS1 and sequesters it to the cytosol. This re-localization of ALAS1 leads to a decrease in mitochondrial volume and impairment of its metabolic potPLoS pathogensAntagonism of ALAS1 by the Measles Virus V protein contributes to degradation of the mitochondrial network and promotes interferon response.PMC9983871IP/SC-15364Ghozlane ASuspene RVolant STangy FVartanian JPRigaud SCaval VCaignard GKhalfi PBerry NRufie CRaymond KAThiers VCombredet CKomarova AVfalseAntagonism of ALAS1 by the Measles Virus V protein contributes to degradation of the mitochondrial network and promotes interferon response.Viruses have evolved countless mechanisms to subvert and impair the host innate immune response. Measles virus (MeV), an enveloped, non-segmented, negative-strand RNA virus, alters the interferon response through different mechanisms, yet no viral protein has been described as directly targeting mitochondria. Among the crucial mitochondrial enzymes, 5'-aminolevulinate synthase (ALAS) is an enzyme that catalyzes the first step in heme biosynthesis, generating 5'-aminolevulinate from glycine and succinyl-CoA. In this work, we demonstrate that MeV impairs the mitochondrial network through the V protein, which antagonizes the mitochondrial enzyme ALAS1 and sequesters it to the cytosol. This re-localization of ALAS1 leads to a decrease in mitochondrial volume and impairment of its metabolic pot2023-01-01T00:00:00Z2023 Feb2026-07-15T01:38:12.417Z2025-04-05T19:16:45.017ZS-EPMC99838713680240610.1371/journal.ppat.1011170