{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T04:32:49Z","timestamp":1783139569929,"version":"3.54.6"},"reference-count":52,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pyridine Nucleotide-Disulfide Oxidoreductase Domain 2 (PYROXD2; previously called YueF) is a mitochondrial inner membrane\/matrix-residing protein and is reported to regulate mitochondrial function. The clinical importance of PYROXD2 has been unclear, and little is known of the protein\u2019s precise biological function. In the present paper, we report biallelic variants in PYROXD2 identified by genome sequencing in a patient with suspected mitochondrial disease. The child presented with acute neurological deterioration, unresponsive episodes, and extreme metabolic acidosis, and received rapid genomic testing. He died shortly after. Magnetic resonance imaging (MRI) brain imaging showed changes resembling Leigh syndrome, one of the more common childhood mitochondrial neurological diseases. Functional studies in patient fibroblasts showed a heightened sensitivity to mitochondrial metabolic stress and increased mitochondrial superoxide levels. Quantitative proteomic analysis demonstrated decreased levels of subunits of the mitochondrial respiratory chain complex I, and both the small and large subunits of the mitochondrial ribosome, suggesting a mitoribosomal defect. Our findings support the critical role of PYROXD2 in human cells, and suggest that the biallelic PYROXD2 variants are associated with mitochondrial dysfunction, and can plausibly explain the child\u2019s clinical presentation.<\/jats:p>","DOI":"10.3390\/ijms23020986","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T08:20:42Z","timestamp":1642407642000},"page":"986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Biallelic Variants in PYROXD2 Cause a Severe Infantile Metabolic Disorder Affecting Mitochondrial Function"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6768-3665","authenticated-orcid":false,"given":"Nicole J.","family":"Van Bergen","sequence":"first","affiliation":[{"name":"Brain and Mitochondrial Research Group, Murdoch Children\u2019s Research Institute, Royal Children\u2019s Hospital, Parkville, VIC 3052, 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Yaplito","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Melbourne, Parkville, VIC 3010, Australia"},{"name":"Department of Metabolic Medicine, Royal Children\u2019s Hospital, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Le Fevre","sequence":"additional","affiliation":[{"name":"Victorian Clinical Genetics Services, Murdoch Children\u2019s Research Institute, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4191-3319","authenticated-orcid":false,"given":"Oliver","family":"Heath","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine, Royal Children\u2019s Hospital, Parkville, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Mignone","sequence":"additional","affiliation":[{"name":"Medical Imaging Department, 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