{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:48:58Z","timestamp":1790646538320,"version":"4.1.0"},"reference-count":201,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["No. NRF-2024-00340086"],"award-info":[{"award-number":["No. NRF-2024-00340086"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Microproteins are small polypeptides translated from short open reading frames (sORFs) that typically encode &lt; 100 amino acids. Advances in ribosome profiling, mass spectrometry, and computational prediction have revealed a growing number of microproteins that play important roles in cellular metabolism, organelle function, and stress adaptation; however, these were considered non-coding or functionally insignificant. At the mitochondrial level, microproteins, such as MTLN (also known as mitoregulin\/MOXI) and BRAWNIN, contribute to lipid oxidation, oxidative phosphorylation efficiency, and respiratory chain assembly. Other microproteins at the endoplasmic reticulum\u2013mitochondria interface, including PIGBOS and several muscle-resident regulators of calcium cycling, show diverse biological contexts in which these microproteins act. A subset of microproteins responds to nutrient availability. For example, SMIM26 modulates mitochondrial complex I translation under serine limitation, and non-coding RNA expressed in mesoderm-inducing cells encoded with peptides facilitates glucose uptake during differentiation, indicating that some microproteins can affect metabolic adaptation through localized translational- or organelle-level mechanisms. Rather than functioning as primary nutrient sensors, these microproteins complement classical nutrient-responsive pathways such as AMP-activated protein kinase-, peroxisome proliferator-activated receptor-, and carbohydrate response element binding protein-mediated signaling. As the catalog of microproteins continues to expand, integrating proteogenomics, nutrient biology, and functional studies will be central to defining their physiological relevance; these integrative approaches will also help reveal their potential applications in metabolic health.<\/jats:p>","DOI":"10.3390\/ijms262411883","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T13:51:46Z","timestamp":1765288306000},"page":"11883","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Microproteins in Metabolic Biology: Emerging Functions and Potential Roles as Nutrient-Linked Biomarkers"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2044-5640","authenticated-orcid":false,"given":"Seong-Hee","family":"Ko","sequence":"first","affiliation":[{"name":"Department of Food and Nutrition, Inha University, 100 Inha-Ro, Michuhol-Gu, Incheon 22212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9558-689X","authenticated-orcid":false,"given":"BeLong","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0828-184X","authenticated-orcid":false,"given":"Dayeon","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Inha University, 100 Inha-Ro, Michuhol-Gu, Incheon 22212, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106781","DOI":"10.1016\/j.isci.2023.106781","article-title":"Microproteins: Overlooked regulators of physiology and disease","volume":"26","author":"Hassel","year":"2023","journal-title":"iScience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1093\/hmg\/6.10.1735","article-title":"Computational methods for the identification of genes in vertebrate genomic sequences","volume":"6","author":"Claverie","year":"1997","journal-title":"Hum. 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